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Tumor Biology |
Myriad Genetics, Inc., Salt Lake City, Utah 84108 [A. K. C. W., Y. C., L. L., P. H., S. G., D. I., B. P., A-M. W., R. S., G. S., A. C., K. L., J. G., B. S., S. V. T., D. H-F. T.], and DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, California 94304 [F. S., K. H., E. L.]
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ABSTRACT |
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 Top ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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INTRODUCTION |
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TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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The SWI/SNF apparatus has been demonstrated to play a role in hormone receptor activation and the transcriptional activation of a number of other genes (reviewed in Ref. 1 ). More recent data using microarray analysis of global gene expression in yeast have demonstrated that SWI/SNF may also be involved in transcriptional repression. Inactivation of the SWI/SNF remodeling complex altered the expression levels of 6% of all of the yeast genes and surprisingly revealed that most were negatively regulated by SWI/SNF (4) . Experiments in many systems now support a model whereby chromatin remodeling complexes facilitate both transcriptional activation and repression via nucleosome mobilization (reviewed in Ref. 3 ).
In mammalian cells it is believed that BRG1 may play an important role in growth control through its physical interaction with the pRb tumor suppressor protein (5 , 6) . Transfection of wild-type BRG1 gene into SW13 adrenal carcinoma cells that lack endogenous BRG1/BRM expression reverted the transformed phenotype of these tumor cells and induced growth arrest in a pRb-dependent fashion (5) . More recent data show that pRb and BRG1/BRM act together to repress transcription of certain E2F target genes required for entry into S phase, such as cyclin A and CDC2 (7 , 8) . Additionally, BRG1 may act to modulate the transcriptional activity of oncogenes such as c-FOS (9) . In this case the repression is believed to be E2F independent, suggesting that BRG1 may modulate transcriptional activity via a number of alternate mechanisms.
Taken together, these data suggest that BRG may play an important role in the regulation of cellular proliferation through transcriptional regulation of key genes required for S phase entry and may therefore act as a tumor suppressor itself. In this study we show that BRG1 is homozygously deleted or mutated in several different cell lines. Reintroduction of BRG1 into these cells causes cell cycle arrest and a flat cell morphology, indicating that loss of BRG1 was important in the development of their transformed phenotype.
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MATERIALS AND METHODS |
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TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Reagents.
Polyclonal antibodies to BRG1, BAF155, and hINI1 were as described in
Ref. 10
, and J1 was a gift from G. Crabtree
(Stanford University, Palo Alto, CA; Ref. 11
). To generate
a specific monoclonal antibody to human BRG1 (8A11) mice were immunized
with a GST5
fusion protein expressing amino acids 1–700 of BRG1 (10)
.
Hybridomas were generated using standard procedures. Antibodies to BRM
were purchased from Santa Cruz Biotechnology (sc-6449) and Transduction
Laboratories (B36320) and to pRb from Santa Cruz Biotechnology (C-20).
A monoclonal antibody to cyclin E, HE172 has been previously described
(10)
.
RNA and DNA Isolation.
Total RNA and genomic DNA were prepared simultaneously using the TRI
Reagent (Molecular Research Center). RNAs were reversed transcribed
with Superscript II (Life Technologies) to generate first-strand cDNAs
that were subsequently PCR amplified.
Radiation Hybrid Mapping.
Radiation hybrid mapping was performed using the Genebridge panel 4
(Human Genome Project, Sanger Center) and the following
BRG1-specific STS primers: 5'-ACTGTCTGCAGCTCCCGTGAA and
5'-CAGCATGGCTCCAGGGGAAGG. These primers were developed from sequences
within exon 2 of the gene and amplified a 106-bp product.
Mutation Screens.
Protocols for the homozygous deletion search and PCR-sequence-based
mutation analyses were as described previously (12)
. All
of the amplifications were done using Platinum Taq DNA polymerase (Life
Technologies). Briefly, each primer pair for STSs 1–6 (Fig. 1B)
was mixed with 30 ng of genomic DNA and subjected to 35
cycles of PCR amplification. The product of STS 7 (Fig. 1A)
was generated by two rounds of sequential PCR using in the first-round
primers 5'-GTGCCCCTGGTTGACTCAAGA and 5'-TTGGGAACTGACTGGCTACAG and then,
in a secondary reaction, two nested primers tailed with M13 forward or
reverse sequences (underlined),
5'-GTTTTCCCAGTCACGACGCAGCCCCTCCCCGACCACCT and
5'AGGAAACAGCTATGACCATAGAGCACGGTCTGTCCACCC.
Product from the secondary reaction was sequenced using a M13 forward
or reverse primer. Similarly, BRG1 cDNA amplicons were
produced by two rounds of sequential PCR using the primers listed in
Table 1
. Five primary A-P amplicons (1, 2, 3, 4, 5)
were developed to span the
gene’s entire ORF. Each primary A-P product was diluted into secondary
reactions containing corresponding nested primer pairs: B-Q, C-R,
D-S, E-T, or F-U. Throughout, PCR artifacts were
dispelled by sequencing independent PCR fragments.
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Immunoprecipitations and immunoblots were performed as previously described (10) . For protein analysis cell pellets were lysed in buffer (250 mM NaCl, 50 mM Tris, pH 8.0, 0.1% NP40) plus protease inhibitors (complete EDTA-free tablets, protease inhibitor cocktail, Boehringer Mannheim). For E1A binding experiments 500 µg cell lysate was mixed with 5 µg GST E1A protein and incubated for 1 h at 4°C. Fifty microliters of 50% slurry of gluthathione agarose beads (Sigma) were added, and samples were incubated for an additional 1 h. The agarose beads were then pelleted by centrifugation, washed extensively with lysis buffer, resuspended in sample buffer, and then loaded on 8% Novex SDS-PAGE gels. After electrophoresis, proteins were transferred to Immobilon poly(vinylidene difluoride) (Millipore) and probed for the presence of pRb using standard Western blotting procedures.
Flat Cell Assays.
For stable transfections ALAB or TSU-Pr1 cells were transfected with 6
µg total plasmid DNA including 2 µg pBJ5.BRG1 using 25 µl
LipofectAMINE reagent (Life Technologies, Inc). pBSK was used as
carrier. Forty-eight h posttransfection cells were trypsinized and
counted, and cells were replated in the presence of puromycin (Sigma)
at 2 µg/ml in complete medium. After 10 days of selection, cells were
fixed overnight in methanol and stained in crystal violet solution (2%
crystal violet in 20% methanol) for 5 h.
FACS Analysis.
Cells were transiently transfected as previously described
(13)
. Briefly, cells were transfected with 5 µg
pBJ5.BRG1, pBJ5BRGK > R, CMVp27, CMVp16, or CMV.CDK2DN plus 1 µg
CMVCD20 using 25 µl LipofectAMINE reagent. pBSK was used as carrier.
Forty-eight h posttransfection, the cells were trypsinized, replated at
lower density, and incubated at 37°C for 18–24 h. Cells were
harvested and stained with 5 µl FITC-conjugated anti-CD20 monoclonal
antibody (Leu-16, Becton Dickinson), on ice for 30 min. The cells were
washed and fixed with 85% ethanol. Cells were stained with propidium
iodide and analyzed by FACS.
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RESULTS |
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TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Mutation Screening.
Homozygous deletion screens were performed using BRG1
gene-specific STSs to amplify fragments from 188 human tumor cell line
genomic DNAs by PCR. Two of the 188 cell lines examined, prostate
carcinoma TSU-Pr1 and lung carcinoma A-427, failed to amplify a product
with a STS designed from the COOH-terminal region of the
BRG1 gene (Fig. 1, A and B)
. To ensure
that failure to detect a PCR product was not because of a sequence
polymorphism, we developed and tested independent flanking STSs that
probed different regions of the gene (Fig. 1, A and B)
. Overall, three contiguous STSs (4, 5, 6)
failed to amplify from TSU-Pr1 genomic DNA (Lanes 3),
whereas STSs 3–6 were absent in A-427 genomic DNA (Lanes
2), indicating that the breakpoints of the deletions in the
two cell lines were different.
In addition to homozygous deletions, another common mechanism for
inactivating tumor suppressor genes involves microlesions, such as
point mutations, in a loss-of-heterozygosity background. Using
overlapping amplicons designed to cover the entire ORF of
BRG1 (Table 1)
, we screened the BRG1 cDNAs from
92 tumor cell lines for sequence alterations. In 2 of the 92 tumor cell
lines, lung NCI-H1299 and prostate DU145 (Fig. 1A
,
Lanes 7 and 8), we observed that the PCR product
of one amplicon was smaller and additionally, that no wild-type product
was detected. Sequence analyses confirmed that both of these shorter
cDNA fragments had eliminated the same 85 bases of the gene’s ORF
(nucleotides 1677–1761), which should result in frameshift mutations.
As a step toward elucidating the molecular events underlying the cDNA
deletions, we mapped the genomic structure of BRG1 (see
"Materials and Methods" for details). Intron-exon mapping showed
that the major form of this gene contains 35 exons (GenBank accession
no. AC006127) and that the 85-base deleted segment of the cDNA observed
in DU145 and NCI-H1299 removes the 3' portion of the 168-base exon 10.
To define the molecular cause of these deletions, primers specific to
the intronic sequences flanking exon 10 were used to amplify genomic
DNA fragments from the two aberrant tumor cell lines. We observed that
the product from DU145 appeared to be wild type in size; however, the
product from NCI-H1299 was smaller (Fig. 1A
, STS 7,
Lane 4). On sequencing, we found a G to T mutation at the
conserved splice donor site of exon 10 in DU145, whereas NCI-H1299
exhibited a 69-base deletion that deletes the same splice donor site
(Fig. 1C)
. Both of these splice site mutations appear to
result in the activation of a cryptic splice donor within exon 10 (Fig. 1
C, 
) an event that would lead to the expression of
frame-shifted BRG1 mRNA. Importantly, we found that
wild-type BRG1 was not detected from either cDNA or genomic
DNA template from either of these cell lines (Fig. 1A)
. In
the screening of the rest of the tumor cell line cDNAs, another
mutation was identified in the breast carcinoma cell line ALAB, where a
C1630T change results in a stop codon to yield a truncated ORF (Table 2)
. In the Hs 700T pancreatic carcinoma cell line, deletion of a single C
base at ORF position 729 was identified, which should cause a
frameshift mutation. In both these cases, wild-type BRG1
mRNA was not detected, indicating loss of heterozygosity.
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there is no expression of wild-type BRG1 in any of the cell
lines containing homozygous mutations in BRG1, consistent
with the lack of mRNA expression. The presence of biallelic
inactivations affecting BRG1 in these cell lines is
consistent with the Knudson two-hit model of inactivation for tumor
suppressor genes during cancer progression (18)
.
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, they all express detectable levels of hINI5/SNF5 and
BAF155, two other core components of the SWI/SNF complex (19
, 20)
. A surprising result, however, was the pattern of BRM
expression in some of the tumor cell lines. In ALAB, SW13, and A427
cells that lacked BRG1 expression, we also failed to detect expression
of its close relative BRM. C33A cells, a cervical carcinoma cell line
previously described to lack BRM expression, has low levels of BRM but
no BRG1 expression using our reagents and methods (21)
.
Lastly, BRM expression levels were generally much lower in cells
lacking BRG expression than those in controls. These results suggest
that BRM expression may also be lost in some instances when
BRG1 is mutated.
pRb Status of BRG1 Mutant Cell Lines.
Work from a number of laboratories has suggested that BRG1 may
function, at least in part, through its physical interaction with the
pRb tumor suppressor protein (5, 6, 7, 8)
. Additionally, recent
work by Zhang et al. proposed a model whereby the
growth-suppressive functions of both pRb and BRG1 are strictly
dependent on one another (8)
. This model predicts that
there may be a reciprocity in BRG1 and RB
mutations in tumor cell lines, given the functional redundancy of
mutation of two genes that function in the same pathway. To test the
BRG1 mutant cell lines for pRb status, lysates were prepared
and subjected to Western blot analysis for pRb expression. ML-1 and
WERI cells were included as positive and negative controls,
respectively (22)
. As can be seen in Fig. 3
A, the major of the BRG1 mutant cell lines express
apparently full-length pRb protein, with the exception of C33A cells
and DU145 cells. To further confirm that the expressed pRb was indeed
wild type, we used a functional assay where the ability of pRb to bind
the viral oncoprotein E1A was examined. To date all spontaneously
occurring RB gene mutations, which do not grossly compromise
pRb stability, are inactive with respect to E1A binding (23
, 24)
. Cell lysates were mixed with a GST fusion protein
expressing adenovirus E1A, and then bound proteins were isolated using
gluthathione agarose beads. As can be seen in Fig. 3B
all of
the cell lines expressing pRb express a functional polypeptide that can
bind E1A, confirming that RB is wild type in these cells.
Thus, 6 of 8 of the BRG1 mutant cell lines are wild type for
RB. The two exceptions are both unusual cases. DU145 cells
are known to have microsatellite instability and contain mutations in
both RB and p16 in addition to the
BRG1 mutation that we have identified (25)
.
C33A cells do not express BRG1 protein, but we have been unable to
detect any homozygous mutation in BRG1 (Ref.
21
).6
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stable transfection of BRG1 into ALAB induced a flat cell phenotype at
high frequency. BRG1-induced growth arrest previously has been
demonstrated for SW13 cells; however, the flat cell induction is
dramatically more efficient in ALAB cells (Fig. 4B
; Refs.
5
, 10
). A similar flattened morphology was observed with
the reintroduction of BRG1 into the prostate cell line TSU-Pr1 (Fig. 4B)
. These results clearly demonstrate that BRG1 can alter
the transformed phenotype of these cells and suggests that loss of
BRG1 may have been important for their immortalization.
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, transient transfection of BRG1 into ALAB cells induces a
substantial G1 arrest as measured by FACS
analysis, comparable with that seen using the CDK inhibitor p27. The
ATPase mutant version of BRG1, K798R, failed to arrest the cells
significantly, suggesting that BRG1 needs to be enzymatically active to
induce growth arrest (11)
. To confirm that it is the
reintroduction of BRG1 that induces the arrest, we also examined the
effects in U20S cells that contain both wild-type BRG1 (and pRb).
Growth arrest was not observed after transfection of BRG1 into U2OS
cells, whereas p27 was equally effective at inducing a growth arrest as
in the ALAB cells. Parallel experiments using the CDK inhibitor p16
gave us surprising results. Although p16 could induce growth arrest in
U20S cells, it had no effect in the ALAB cells. Similar observations
have been reported by Zhang et al. in SW13 cells
(8)
. These findings support the model that the RB pathway
is functionally defective in BRG minus cells (8)
.
Consistent with this notion, when BRG1 was reintroduced into ALAB
cells, addition of p16 had a slight synergistic effect, resulting in a
more efficient G1 arrest. Experiments in pRb
minus cells such as C33A (see Fig. 5
) demonstrate that BRG1 alone is
insufficient to induce growth arrest in a cell lacking pRb. Work for
others has shown that reintroduction of pRb and BRG1 into these cells
will induce growth arrest (8
, 26)
.
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). Western blot analysis revealed that Hs578T does not
express BRG1 protein, whereas all of the other point mutations did not
appear to affect protein expression grossly, although BRG1 levels
appeared to be generally lower than other cell lines that we have
examined (Fig. 6
and data not shown).
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, several of these cell lines appear to have
defective SWI-SNF complexes. Particularly interesting was that we
failed to detect a complex between BRG1 and cyclin E in HCT116 cells,
the cell line that displayed apparent loss-of-heterozygosity in the
mutation screen but retained BRG1 protein expression. As predicted, we
failed to detect a complex between BRG1 and cyclin E in Hs578T cells.
These preliminary data suggest that some of the point mutations may
lead to defective BRG1, providing an additional mechanism by which BRG1
function may be altered in human cancers. |
DISCUSSION |
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TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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) may provide another mechanism by which BRG1 activity can be modified
in human cancers. Because the activity of BRG1 is poorly understood at
the mechanistic level these point mutants may provide a useful tool in
elucidating BRG1 function.
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In addition to loss of BRG1 expression, we also observed loss of BRM expression in a concordant fashion in some tumor cell lines. It is of interest to note that in mice homozygously deleted for BRM, BRG1 is up-regulated and may substitute for some functions allowing for viability (27) , whereas loss of BRG1 is believed to be lethal (28) . It will be interesting to learn whether this loss in viability is attributable to the additional loss of BRM expression in these knockout cells.
It is tempting to speculate that the role of BRG1 in cancer progression is primarily executed through its regulation of tumor suppressors such as pRb. Our data suggest that there may be a certain amount of reciprocity between mutations in BRG1 and RB, because pRb is wild type in the major of BRG1 mutant cell lines. Again, analysis of a larger number of samples will provide confirmation of this model. It will be important to fully elucidate the relationship of BRG1 with the p16/pRb pathway. Our initial experiments show that p16 is unable to arrest a BRG1 mutant cell line, suggesting that these two molecules may function in the same pathway. Work from the Dean laboratory strongly supports this model (8) . Despite these correlations, it remains to be established whether all of the BRG1 functions are mediated by pRb and vice versa.
Recently, another component of the SWI-SNF complex, hSNF5/INI1, localized on human chromosome 22q11.2, has been found to be mutated at significant frequency in malignant pediatric rhabdoid tumors (29) and chronic myeloid leukemias (30) . Taken together, these results indicate that transcriptional regulation through ATP-dependent chromatin remodeling by the SWI-SNF complex is critical in tumorigenesis. Additional studies will be needed to establish whether other components of the SWI-SNF complex are mutated during cellular transformation.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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1 Present address: Sankyo Pharma Research
Institute, 4250 Executive Square, Suite 420, La Jolla, CA 92037. 
2 D. H-F. T. and E. L. contributed equally to
this work.
3 Present address: Arcaris, Inc., 615 Arapeen
Drive, Suite 300, Salt Lake City, UT 84108.
4 To whom requests for reprints should be
addressed, at DNAX Research Institute, 901 California Avenue, Palo
Alto, CA 94304-1104. Phone: (650) 496-1257; Fax: (650) 496-1200;
E-mail: lees{at}dnax.org
5 The abbreviations used are: GST,
glutathione S-transferase; STS, sequence tagged-site;
FACS, fluorescence-activated cell sorter; ORF, open reading frame; HRP,
horseradish peroxidase; ECL, enhanced chemiluminescence.
Received 7/12/00. Accepted 9/ 8/00.
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REFERENCES |
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TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Z. Ma, M. J. Chang, R. Shah, J. Adamski, X. Zhao, and E. N. Benveniste Brg-1 Is Required for Maximal Transcription of the Human Matrix Metalloproteinase-2 Gene J. Biol. Chem., October 29, 2004; 279(44): 46326 - 46334. [Abstract] [Full Text] [PDF]
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A. H. Lund and M. van Lohuizen Epigenetics and cancer Genes & Dev., October 1, 2004; 18(19): 2315 - 2335. [Abstract] [Full Text] [PDF]
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 C. B. Zraly, D. R. Marenda, and A. K. Dingwall SNR1 (INI1/SNF5) Mediates Important Cell Growth Functions of the Drosophila Brahma (SWI/SNF) Chromatin Remodeling Complex Genetics, September 1, 2004; 168(1): 199 - 214. [Abstract] [Full Text] [PDF]
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S. Medjkane, E. Novikov, I. Versteege, and O. Delattre The Tumor Suppressor hSNF5/INI1 Modulates Cell Growth and Actin Cytoskeleton Organization Cancer Res., May 15, 2004; 64(10): 3406 - 3413. [Abstract] [Full Text] [PDF]
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 M. Hirano, Y. Kikuchi, S. Nisitani, A. Yamaguchi, A. Satoh, T. Ito, H. Iba, and K. Takatsu Bruton's tyrosine kinase (Btk) enhances transcriptional co-activation activity of BAM11, a Btk-associated molecule of a subunit of SWI/SNF complexes Int. Immunol., May 1, 2004; 16(5): 747 - 757. [Abstract] [Full Text] [PDF]
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C. Muller, C. F. Calkhoven, X. Sha, and A. Leutz The CCAAT Enhancer-binding Protein {alpha} (C/EBP{alpha}) Requires a SWI/SNF Complex for Proliferation Arrest J. Biol. Chem., February 20, 2004; 279(8): 7353 - 7358. [Abstract] [Full Text] [PDF]
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I. Oruetxebarria, F. Venturini, T. Kekarainen, A. Houweling, L. M. P. Zuijderduijn, A. Mohd-Sarip, R. G. J. Vries, R. C. Hoeben, and C. P. Verrijzer p16INK4a Is Required for hSNF5 Chromatin Remodeler-induced Cellular Senescence in Malignant Rhabdoid Tumor Cells J. Biol. Chem., January 30, 2004; 279(5): 3807 - 3816. [Abstract] [Full Text] [PDF]
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K. B. Hendricks, F. Shanahan, and E. Lees Role for BRG1 in Cell Cycle Control and Tumor Suppression Mol. Cell. Biol., January 1, 2004; 24(1): 362 - 376. [Abstract] [Full Text] [PDF]
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R. Vernell, K. Helin, and H. Muller Identification of Target Genes of the p16INK4A-pRB-E2F Pathway J. Biol. Chem., November 14, 2003; 278(46): 46124 - 46137. [Abstract] [Full Text] [PDF]
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S. Pal, R. Yun, A. Datta, L. Lacomis, H. Erdjument-Bromage, J. Kumar, P. Tempst, and S. Sif mSin3A/Histone Deacetylase 2- and PRMT5-Containing Brg1 Complex Is Involved in Transcriptional Repression of the Myc Target Gene cad Mol. Cell. Biol., November 1, 2003; 23(21): 7475 - 7487. [Abstract] [Full Text] [PDF]
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T. W. Marshall, K. A. Link, C. E. Petre-Draviam, and K. E. Knudsen Differential Requirement of SWI/SNF for Androgen Receptor Activity J. Biol. Chem., August 15, 2003; 278(33): 30605 - 30613. [Abstract] [Full Text] [PDF]
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Z. Nie, Z. Yan, E. H. Chen, S. Sechi, C. Ling, S. Zhou, Y. Xue, D. Yang, D. Murray, E. Kanakubo, et al. Novel SWI/SNF Chromatin-Remodeling Complexes Contain a Mixed-Lineage Leukemia Chromosomal Translocation Partner Mol. Cell. Biol., April 15, 2003; 23(8): 2942 - 2952. [Abstract] [Full Text] [PDF]
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D. N. Reisman, J. Sciarrotta, W. Wang, W. K. Funkhouser, and B. E. Weissman Loss of BRG1/BRM in Human Lung Cancer Cell Lines and Primary Lung Cancers: Correlation with Poor Prognosis Cancer Res., February 1, 2003; 63(3): 560 - 566. [Abstract] [Full Text] [PDF]
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K. Roy, I. L. de la Serna, and A. N. Imbalzano The Myogenic Basic Helix-Loop-Helix Family of Transcription Factors Shows Similar Requirements for SWI/SNF Chromatin Remodeling Enzymes during Muscle Differentiation in Culture J. Biol. Chem., September 6, 2002; 277(37): 33818 - 33824. [Abstract] [Full Text] [PDF]
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R. Mudhasani and J. D. Fontes The Class II Transactivator Requires brahma-Related Gene 1 To Activate Transcription of Major Histocompatibility Complex Class II Genes Mol. Cell. Biol., July 15, 2002; 22(14): 5019 - 5026. [Abstract] [Full Text] [PDF]
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T. Mizutani, T. Ito, M. Nishina, N. Yamamichi, A. Watanabe, and H. Iba Maintenance of Integrated Proviral Gene Expression Requires Brm, a Catalytic Subunit of SWI/SNF Complex J. Biol. Chem., May 3, 2002; 277(18): 15859 - 15864. [Abstract] [Full Text] [PDF]
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H. R. Moinova, W.-D. Chen, L. Shen, D. Smiraglia, J. Olechnowicz, L. Ravi, L. Kasturi, L. Myeroff, C. Plass, R. Parsons, et al. HLTF gene silencing in human colon cancer PNAS, April 2, 2002; 99(7): 4562 - 4567. [Abstract] [Full Text] [PDF]
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K. E. Neely, A. H. Hassan, C. E. Brown, L. Howe, and J. L. Workman Transcription Activator Interactions with Multiple SWI/SNF Subunits Mol. Cell. Biol., March 15, 2002; 22(6): 1615 - 1625. [Abstract] [Full Text] [PDF]
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M. W. Strobeck, D. N. Reisman, R. W. Gunawardena, B. L. Betz, S. P. Angus, K. E. Knudsen, T. F. Kowalik, B. E. Weissman, and E. S. Knudsen Compensation of BRG-1 Function by Brm. INSIGHT INTO THE ROLE OF THE CORE SWI{middle dot}SNF SUBUNITS IN RETINOBLASTOMA TUMOR SUPPRESSOR SIGNALING J. Biol. Chem., February 8, 2002; 277(7): 4782 - 4789. [Abstract] [Full Text] [PDF]
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H. Kato, A. Tjernberg, W. Zhang, A. N. Krutchinsky, W. An, T. Takeuchi, Y. Ohtsuki, S. Sugano, D. R. de Bruijn, B. T. Chait, et al. SYT Associates with Human SNF/SWI Complexes and the C-terminal Region of Its Fusion Partner SSX1 Targets Histones J. Biol. Chem., February 8, 2002; 277(7): 5498 - 5505. [Abstract] [Full Text] [PDF]
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P. Asp, M. Wihlborg, M. Karlen, and A.-K. O. Farrants Expression of BRG1, a human SWI/SNF component, affects the organisation of actin filaments through the RhoA signalling pathway J. Cell Sci., January 7, 2002; 115(13): 2735 - 2746. [Abstract] [Full Text] [PDF]
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C. J. Guidi, A. T. Sands, B. P. Zambrowicz, T. K. Turner, D. A. Demers, W. Webster, T. W. Smith, A. N. Imbalzano, and S. N. Jones Disruption of Ini1 Leads to Peri-Implantation Lethality and Tumorigenesis in Mice Mol. Cell. Biol., May 15, 2001; 21(10): 3598 - 3603. [Abstract] [Full Text]
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H. R. Moinova, W.-D. Chen, L. Shen, D. Smiraglia, J. Olechnowicz, L. Ravi, L. Kasturi, L. Myeroff, C. Plass, R. Parsons, et al. HLTF gene silencing in human colon cancer PNAS, April 2, 2002; 99(7): 4562 - 4567. [Abstract] [Full Text] [PDF]
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106/ml density and
grown in the presence of puromycin for 10 days. A,
representative flat cells induced by BRG1 transfection; x40;
B, cells were stained with crystal violet and counted.
*, total number of flat cells in 3 x 1 cm.
