| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Advances in Brief |
Departments of Thoracic/Head and Neck Medical Oncology [W. W., W. K. H., L. M.] and Pathology [B. L. K.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, and Hamon Center for Therapeutic Oncology Research, The University of Texas Southwestern Medical Center, Dallas, Texas 75235 [M. L. P., A. E. G., J. D. M.]
 |
ABSTRACT |
|---|
 Top ABSTRACT IntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
|
Introduction |
|---|
|
TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
DMBT1 was cloned through a representational differential analysis that is used to identify potential homozygous deletions in target genomic DNA (6) . The gene was localized to 10q25.3–q26.1, a region with frequent LOH3 in many types of human cancers including lung cancer (7, 8, 9, 10) . Intragenic homozygous deletions of DMBT1 were found in 23–38% of medulloblastoma and glioblastoma multiforme cell lines and primary glioblastoma multiforme (6 , 11) . Interestingly, loss of DMBT1 gene expression was found in 80% of these tumor cell lines (6) . These data suggest that DMBT1 is a candidate tumor suppressor gene and may play an important role in brain tumorigenesis. Deduced DMBT1 protein contains at least nine SRCR domains that allow the gene to be classified as a new member of the SRCR superfamily. Some members of this superfamily have been linked to initiation of cell proliferation and differentiation in immune system tissue and other tissues (12, 13, 14, 15) or have been associated with the polarity of epithelial cells (16) . A leader sequence present in DMBT1 protein, together with the presence of SRCR, CUB, and ZP domains and N-glycosylation sites, suggests that DMBT1 is likely a secreted or membrane protein (12, 13, 14, 15, 16, 17) . In adult humans, DMBT1 is highly expressed only in lung and small intestine, suggesting that the protein has an important role in these tissues (6) . Furthermore, the gene is located within one of the two minimally deleted regions at chromosome 10q identified in primary SCLCs (10) , raising the possibility that the gene may be also important in lung tumorigenesis. In this study, we investigated whether DMBT1 is altered in lung cancer and found an intragenic homozygous deletion of the gene in 10% of the SCLC cell lines tested and lack of the gene expression in all of the SCLC cell lines tested. Furthermore, more than 40% of NSCLC cell lines and primary NSCLCs also lacked DMBT1 expression. The identification of a potential point mutation in the gene in a NSCLC cell line further supports the notion that DMBT1 may play an important role in lung tumorigenesis.
|
Materials and Methods |
|---|
|
TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
DNA and RNA Extraction and cDNA Synthesis.
Genomic DNA was isolated from SCLC and NSCLC cell lines by proteinase-K digestion (0.1 mg/ml) at 50°C overnight, followed by phenol/chloroform extraction and ethanol precipitation. For fresh tissues, samples were sectioned using a cryostat microtome. Selected sections were stained with H&E and reviewed for the presence of tumor cells. Only tumor samples containing about 70% or more tumor cells and normal lung tissues without tumor cells were used for DNA extraction. The proteinase-K digestion and DNA purification methods are the same as those used for cell lines. For total RNA extraction from cell lines, the cell pellets were quickly suspended in RNAzol B solution (Biotecx Laboratories, Inc., Houston, TX) to lyse the cells. For fresh tissue samples, 20–50 mg of tissue were mechanically homogenized in 1 ml of RNAzol B solution (Biotecx Laboratories, Inc., Houston, TX). Five µg of total RNA from each sample were then used to synthesize single-strand cDNA using SUPERSCRIPT II RNase H- reverse transcriptase (Life Technologies, Grand Island, NY), following the manufacturer’s protocol. The synthesized cDNA was used immediately for PCR amplification or stored at -20°C for further analysis.
PCR Analysis.
PCR for genomic DNA was conducted using a 20-ng genomic DNA sample as described previously (10)
. Primer sets used for detecting deletions of DMBT1 gene were 36k, g14, g14ext, and 101n as reported previously (6)
. A primer set for ß-actin was used to amplify a 415-bp fragment as a control for DNA quality. The primer sequences for the ß-actin fragment were 5'-CTCACATCGTGCCCATCTAT-3' (sense) and 5'-GATCCTTGCGAATATCCACA-3' (antisense). For multiplex PCR analysis, one primer set for a target molecule was used together with the primer set for the ß-actin fragment. To amplify cDNA, each of the PCR reactions was performed in a 25-µl volume containing 0.5 µl of reverse transcriptase reaction mixture, 3% DMSO, 1.5 mM of deoxynucleotide triphosphate, 6.7 mM of MgCl2, 16.6 mM of (NH4)2SO4, 67 mM of Tris, 10 mM of ß-mercaptoethanol, 6.7 µM EDTA, 2.5 units of Taq polymerase (Life Technologies), and 0.4 µM each of the primers. Reactions without templates were used as negative controls to rule out the possibility of contamination. Thermal cycling was performed in a temperature cycler (Hybaid; Omnigene, Woodbridge, NJ) in 500-µl plastic tubes for one initial cycle of denaturation at 95°C for 2 min, followed by 30 cycles of denaturation at 95°C for 30 s, annealing at 59°C for 45 s, extension at 70°C for 1 min, and a final elongation step at 70°C for 5 min. The PCR products were then separated in a 2% agarose gel containing 0.5 µg/ml ethidium bromide. Primers used for cDNA amplification are as follows: DMBT-1 A/2AS, 5'-GCAGCAGAAATATACCACCC-3' (sense) and 5'-CCACCCACCTGTAGATAG-3' (antisense); DMBT-1 4S/4AS, 5'-CAGGAGCTATCTCCAATC-3' (sense) and 5'-ACACCAAGAGGAACATCC-3' (antisense).
Sequence Analysis.
After PCR, we excised the bands we were interested in from a 1.5% agarose gel and purified them using Qiaquick resin columns (Qiagen, Valencia, CA). Between 10 and 15 ng of DNA per sample were used for each direct sequencing reaction containing a primer labeled with [
-33P]ATP and amplified by PCR for 35 cycles using the AmpliCycle sequencing kit (Perkin-Elmer, Branchburg, NJ) according to the manufacturer’s protocol. Each amplified product (3 µl) was run on a 6% long-range gel (FMC BioProducts, Rockland, ME) and exposed to film. RT-PCR and sequencing primers for DMBT1 cDNA are as follows: DMBT-1 S1, 5'-GCTA-GGTACCTATAAATGTC-3'; DMBT1 AS1, 5'-TCTTCACTATGGCCACAG-3'; DMBT-1 S2, 5'-TTGTCCTGGATGATGTGC-3'; DMBT-1 AS2, 5'-AACACACTTAGCA-TTGTTGG-3; DMBT-1 S3, 5'-ATTGTGGTGGCT-TCTTATTC-3'; DMBT-1 AS3, 5'-ACCAG-GTTCGGCGTTATC-3'; DMBT-1 S4, 5'-CAGGAGCTATCTCCAATC-3'; DMBT-1 AS4, 5'-ACACCAAGAGGAACATCC-3'; DMBT-1 AF, 5'-GCAGCAGAAATATACCACCC-3'; and DMBT-1 BR, 5'-TCCTGAACCCTGGCCAAA-3'.
LOH Analysis.
Fifty ng of DNA were used in each PCR amplification. The microsatellite markers used were D10S209 and D10S587 (Research Genetics, Huntsville, AL). For PCR amplification, one of the primers for each marker was end-labeled with [-32P]ATP (4500 Ci/mmol; ICN Biomedicals, Costa Mesa, CA) and T4 DNA polynucleotide kinase (New England Biolabs, Beverly, MA). PCR reactions were carried out in a 12.5-µl volume containing 3% DMSO, 200 µM of deoxynucleotide triphosphate, 1.5 mM MgCl2, 0.4 µM of PCR primers including 0.01 µM [-32P] labeled primer, and 0.5 unit of Taq DNA polymerase (Life Technologies, Inc.). DNA was amplified for 35 cycles at 95°C for 30 s, 56–60°C for 60 s, and 70°C for 60 s, followed by a 5-min extension at 70°C in a temperature cycler (Hybaid; Omnigene) in 500-µl plastic tubes. PCR products were separated on a 7% polyacrylamide-urea-formamide gel and then exposed to X-ray film. LOH was defined as a >50% reduction of intensity by visual inspection in one of the two alleles as compared with that seen in the corresponding normal control.
|
Results |
|---|
|
TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
. Twenty primary NSCLC tumors (10 adenocarcinomas and 10 squamous cell carcinomas) were also analyzed for DMBT1 expression by semiquantitative multiplex PCR in which ß-actin was used as an internal control for both cDNA quality and efficiency of PCR amplification. DMBT1 expression was greatly reduced in nine (45%) tumors (four adenocarcinomas and five squamous cell carcinomas) compared with DMBT1 expression in paired normal lung tissues (Fig. 1C)
, suggesting that gene expression was lost in these primary tumors.
|
65-kb fragment of DMBT1 (6)
were used to screen these tumor cell lines. A primer set for the ß-actin genomic DNA fragment was used as an internal control in each PCR reaction. Homozygous deletion was detected in 4 (10%) SCLC cell lines (H711, H889, H1450, and H1963) at g14 (Fig. 2A)
. Because g14 is located between 36k and 101n, which were not homozygously deleted in these four tumor cell lines, the homozygous deletions should be smaller than 65 kb. No homozygous deletion was found in any of the 14 NSCLC cell lines tested. To rule out the possibility that the lack of PCR amplification was due to a rare nucleotide polymorphism within the primers used for g14, we tested another primer set, g14ext, which amplifies a genomic DNA fragment close to g14. DNA also could not be amplified by g14ext in the four cell lines also showing homozygous deletion at g14 (Fig. 2B)
, confirming the existence of intragenic homozygous deletions in DMBT1 in these tumor cell lines.
|
To determine whether there are mutations in DMBT1 that play a role in its inactivation, we sequenced the coding region of DMBT1 in eight NSCLC cell lines expressing the gene. Four nucleotide substitutions were identified in these cell lines compared with the published DMBT1 cDNA sequence (GenBank accession number AJ000342). One substitution (nucleotide 5227 G
A) was identified at the 3' end of the gene in these lines (Calu-1, H1792, and SK-MES-1) without a change in the encoded amino acid. The other three nucleotide substitutions were found at the 5' end of the gene with amino acid changes also present. One substitution is located at codon 42. This codon was originally determined to be glutamine, derived from a coding sequence CAA (GenBank Accession Number AJ000342). However, based on our sequencing analysis of DMBT1 cDNA from 50 individuals, the coding for this codon appears to be ACA encoding a threonine residue. A nucleotide substitution changed the codon from ACA to CCA, resulting in the threonine to proline substitution that was observed in four cell lines (Table 1)
. Another substitution was identified at codon 54 in the same four cell lines (Table 1)
. The coding sequence for this codon was changed from TTG to TCG, resulting in an amino acid change from a leucine to a serine. Finally, a substitution was found at codon 52 in one cell line (Calu-1). The coding sequence TCG was changed to TGG, resulting in an amino acid substitution from a serine to a tryptophan (Fig. 3)
.
|
|
proline substitution at codon 42 was present in 8 (40%) of the 20 NSCLC tumors and in their corresponding normal lung tissues (Table 1)
. This substitution was also found in 6 (27%) of the 22 normal lung tissues from patients with other types of malignancies. The leucineserine substitution at codon 54 was found in the same tumor and normal tissue specimens exhibiting the codon 42 substitution. Thus, we think that these two substitutions represent frequent, linked polymorphisms. However, the serinetryptophan substitution at codon 52 was not observed in any of the specimens from the 42 unrelated individuals tested and seven cell lines studied.
We further performed microsatellite analysis to determine potential LOH at the DMBT1 region in the 20 primary NSCLC tumors in which DMBT1 expression had been analyzed using two microsatellite markers flanking the gene. LOH at the locus was found in 10 (50%) of the 20 tumors. Interestingly, 8 (80%) of the 10 tumors with LOH at the locus had reduced DMBT1 gene expression, whereas the other two tumors with LOH had normal amounts of DMBT1 expression (Table 1)
. Statistical analysis showed that tumors with LOH at DMBT1 locus have a significantly higher rate of lack of DMBT1 expression than those without LOH at the locus (P = 0.005 by Fisher’s exact test).
|
Discussion |
|---|
|
TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
The study presented in this report is the first demonstrating that DMBT1 is also altered frequently in lung cancer. The abnormalities exist not only in tumor cell lines but also in primary tumors. We found a similar rate (45%) of loss of DMBT1 expression in both NSCLC cell lines and primary NSCLC specimens. The discordance between the frequency of homozygous deletions (10% in SCLC and none in NSCLC) and the lack of DMBT1 expression (100% in SCLC and 43% in NSCLC) in lung cancer cell lines suggests that other, yet to be identified mechanisms play a role in the inactivation of the gene. However, it is unlikely that methylation in the promoter region of DMBT1 gene plays an important role because the gene is not GC-rich in sequence content, and a demethylation treatment could not restore DMBT1 expression. However, we cannot exclude the possibility that small deletions exist and are located within DMBT1 but away from regions we examined. It is interesting that most of the primary NSCLC tumors exhibiting lack of DMBT1 expression also lost one of the DMBT1 alleles (LOH), whereas LOH was rare in tumors expressing normal amounts of DMBT1 (P = 0.005; Table 1
), suggesting that LOH plays an important role in inactivating DMBT1. Further studies are required to study subtle alterations within the gene and to identify molecules that control the gene’s expression.
DMBT1 is considered a member of the SRCR superfamily because at least nine SRCR domains are present in its predicted protein sequence. It also contains two CUB domains and one ZP domain. It is interesting that a unique domain with 20–23 amino acid residues (known as SID, for SRCR interspersed domain) is located between every SRCR domain (6)
. In the mouse, the structure of CRP-ductin is very similar to that of DMBT1, with eight SRCR domains, 5 CUB domains, and one ZP domain (15)
. A unique domain with high homology was also found between every SRCR domain in CRP-ductin; it is known as CRP. The 
form of the protein contains a short transmembrane domain and a cytoplasmic domain, whereas the ß form lacks these domains (15)
. In fetal lung tissue, there are three DMBT1 mRNA species of 8.0, 7.5, and 6.0 kb. The sequence reported previously was from the smallest transcript (6)
. Therefore, it is possible that the larger transcripts of DMBT1 contain more coding sequences for a transmembrane and a cytoplasmic domain as demonstrated in the mouse CRP-ductin form. Alternatively, more SRCR domains are present in the larger form of DMBT1. Nevertheless, the lack of gene expression was detected using primers for both the 3' end and the 5' end of the DMBT1 cDNA sequence in this study, indicating that none of these potential isoforms were expressed in these lung tumors.
Previous studies suggest that some of the SRCR superfamily members play a role in cell differentiation (14
, 15)
. Thus, it is possible that the lack of DMBT1 expression results in the loss of epithelial cell differentiation. However, we did not observe clear association between loss of DMBT1 expression and tumor differentiation status or squamous versus adenocarcinoma histology (Table 1)
.
We have identified three amino acid substitutions in DMBT1 at a narrowed NH2-terminal region in lung cancer cell lines and primary tumors. The region contains about 70 amino acids and has no homology to any known protein. Although these substitutions represent nonconservative amino acid changes, two of the substitutions were found in both primary NSCLC tumors and in the corresponding normal lung tissues in 40% of cases analyzed, indicating they are likely to be examples of polymorphism. These polymorphisms are probably also common in patients with other types of cancers (27%). We are presently unable to examine the frequency of these nucleotide changes in a normal population because DMBT1 is not expressed in peripheral lymphocytes, and the genomic sequence of DMBT1 is not yet available. Therefore, we cannot exclude the possibility that these changes may have functional consequences in tumorigenic processes and may be enriched in patients with cancer as a germ-line alteration predisposing to cancer development. The other amino acid substitution at codon 52 was found in only one NSCLC cell line but not in any of the other tumor cell lines, primary tumors, and normal tissues from 49 unrelated individuals, suggesting this substitution may be a somatic mutation. However, this hypothesis requires confirmation by functional analysis in future studies. Thus, it will be interesting to see how replacing wild-type DMBT1 in our tumor cell lines with homozygous deletions compares with a DMBT1 gene with the codon 42 and 54 substitutions.
In summary, we have demonstrated that expression of DMBT1 is frequently lost in lung cancer, particularly in SCLC. We found that intragenic homozygous deletions of DMBT1 exist in a fraction of SCLC cell lines and that LOH status at the DMBT1 region was significantly associated with reduced expression of DMBT1 in primary NSCLC tumors. We also identified three nucleotide substitutions in DMBT1 resulting in nonconservative amino acid changes, including one potential point mutation. These data support the hypothesis that DMBT1 is a tumor suppressor gene and that it plays an important role in lung tumorigenesis.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
1 Supported in part by American Cancer Society Grant RPG-98-054, National Cancer Institute Grants PO1 CA74173 and Lung SPORE Grant CA 70907, and NIH Fellowship Training Grant T32 CA 66187. W. K. H. is an American Cancer Society Clinical Research Professor. 
2 To whom requests for reprints should be addressed, at Molecular Biology Laboratory, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: (713) 792-6363; Fax: (713) 796-8865; E-mail: lmao{at}notes.madcc.tmc.edu
3 The abbreviations used are: LOH, loss of heterozygosity; SCLC, small cell lung cancer; NSCLC, non-small cell lung cancer; RT-PCR, reverse transcription-PCR; STS, specific tag sequence; SRCR, scavenger receptor cysteine-rich; CUB, complement subcomponents Clr/Cls, Uegf, Bmp1; ZP, zona pellucida.
Received 12/14/98. Accepted 3/ 2/99.
|
REFERENCES |
|---|
|
TopABSTRACTIntroductionMaterials and MethodsResultsDiscussionREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  A. C. Blackburn, L. Z. Hill, A. L. Roberts, J. Wang, D. Aud, J. Jung, T. Nikolcheva, J. Allard, G. Peltz, C. N. Otis, et al. Genetic Mapping in Mice Identifies DMBT1 as a Candidate Modifier of Mammary Tumors and Breast Cancer Risk Am. J. Pathol., June 1, 2007; 170(6): 2030 - 2041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Ghosh and G. J. Duigou Decreased Replication Ability of E1-Deleted Adenoviruses Correlates with Increased Brain Tumor Malignancy Cancer Res., October 1, 2005; 65(19): 8936 - 8943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Kang, O. Nielsen, C. Fenger, G. Leslie, U. Holmskov, and K. B.M. Reid Induction of DMBT1 expression by reduced ERK activity during a gastric mucosa differentiation-like process and its association with human gastric cancer Carcinogenesis, June 1, 2005; 26(6): 1129 - 1137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Meuwissen and A. Berns Mouse models for human lung cancer Genes & Dev., March 15, 2005; 19(6): 643 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tynan, E. Pacia, D. Haynes-Johnson, D. Lawrence, M. R. D'Andrea, J.-Z. Guo, S. Lundeen, and G. Allan The Putative Tumor Suppressor Deleted in Malignant Brain Tumors 1 Is an Estrogen-Regulated Gene in Rodent and Primate Endometrial Epithelium Endocrinology, March 1, 2005; 146(3): 1066 - 1073. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F.J. Bikker, J.E. van der Wal, A.J.M. Ligtenberg, J. Mollenhauer, J.M.A. de Blieck-Hogervorst, I. van der Waal, A. Poustka, and A.V. Nieuw Amerongen Salivary Agglutinin/DMBT1SAG Expression is Up-regulated in the Presence of Salivary Gland Tumors J. Dent. Res., July 1, 2004; 83(7): 567 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Z. Kristiansen, J. Bunkenborg, M. Gronborg, H. Molina, P. J. Thuluvath, P. Argani, M. G. Goggins, A. Maitra, and A. Pandey A Proteomic Analysis of Human Bile Mol. Cell. Proteomics, July 1, 2004; 3(7): 715 - 728. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Al-Awqati, S. Vijayakumar, and J. Takito Terminal Differentiation of Epithelia from Trophectoderm to the Intercalated Cell: The Role of Hensin J. Am. Soc. Nephrol., June 1, 2003; 14(90001): S16 - 21. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sasaki, R. A. Betensky, J. G. Cairncross, and D. N. Louis DMBT1 Polymorphisms: Relationship to Malignant Glioma Tumorigenesis Cancer Res., March 1, 2002; 62(6): 1790 - 1796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.J. Bikker, A.J.M. Ligtenberg, J.E. van der Wal, P.A.M. van den Keijbus, U. Holmskov, E.C.I. Veerman, and A.V. Nieuw Amerongen Immunohistochemical Detection of Salivary Agglutinin/gp-340 in Human Parotid, Submandibular, and Labial Salivary Glands J. Dent. Res., February 1, 2002; 81(2): 134 - 139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Mollenhauer, S. Herbertz, B. Helmke, G. Kollender, I. Krebs, J. Madsen, U. Holmskov, K. Sorger, L. Schmitt, S. Wiemann, et al. Deleted in Malignant Brain Tumors 1 Is a Versatile Mucin-like Molecule Likely to Play a Differential Role in Digestive Tract Cancer Cancer Res., December 1, 2001; 61(24): 8880 - 8886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sasaki, M. C. Zlatescu, R. A. Betensky, Y. Ino, J. G. Cairncross, and D. N. Louis PTEN Is a Target of Chromosome 10q Loss in Anaplastic Oligodendrogliomas and PTEN Alterations Are Associated with Poor Prognosis Am. J. Pathol., July 1, 2001; 159(1): 359 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Hikita, S. Vijayakumar, J. Takito, H. Erdjument-Bromage, P. Tempst, and Q. Al-Awqati Induction of Terminal Differentiation in Epithelial Cells Requires Polymerization of Hensin by Galectin 3 J. Cell Biol., December 11, 2000; 151(6): 1235 - 1246. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-X. Liu, S. Musco, N. M. Lisitsina, E. Forgacs, J. D. Minna, and N. A. Lisitsyn LRP-DIT, a Putative Endocytic Receptor Gene, Is Frequently Inactivated in Non-Small Cell Lung Cancer Cell Lines Cancer Res., April 1, 2000; 60(7): 1961 - 1967. [Abstract] [Full Text]
|
|
|
|
|
|
J. Mollenhauer, S. Herbertz, U. Holmskov, M. Tolnay, I. Krebs, A. Merlo, H. D. Schrøder, D. Maier, F. Breitling, S. Wiemann, et al. DMBT1 Encodes a Protein Involved in the Immune Defense and in Epithelial Differentiation and Is Highly Unstable in Cancer Cancer Res., March 1, 2000; 60(6): 1704 - 1710. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. M. Fong, Y. Sekido, and J. D. Minna MOLECULAR PATHOGENESIS OF LUNG CANCER J. Thorac. Cardiovasc. Surg., December 1, 1999; 118(6): 1136 - 1152. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Holmskov, J. Mollenhauer, J. Madsen, L. Vitved, J. Gronlund, I. Tornoe, A. Kliem, K. B. M. Reid, A. Poustka, and K. Skjodt Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D PNAS, September 14, 1999; 96(19): 10794 - 10799. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
