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Advances in Brief |
Department of Carcinogenesis, University of Texas, M. D. Anderson Cancer Center, Smithville, Texas 78957
The important role played by the sex hormone estrogen in disease and
physiological processes has been well documented. However, the
mechanisms by which this hormone elicits many of its normal as well as
pathological effects are unclear. To identify both known and unknown
genes that are regulated by or associated with estrogen action, we
performed serial analysis of gene expression on estrogen-responsive
breast cancer cells after exposure to this hormone. We examined
approximately 190,000 mRNA transcripts and monitored the expression
behavior of 12,550 genes. Expression levels for the vast majority of
those transcripts were observed to remain constant upon 17ß estradiol
(E2) treatment. Only approximately 0.4% of the genes
showed an increase in expression of 
3-fold by 3 h
post-E2 treatment. We cloned five novel genes
(E2IG1-5), which were observed
up-regulated by the hormonal treatment. Of these the most highly
induced transcript, E2IG1, appears to be a novel member
of the family of small heat shock proteins. The E2IG4
gene is a new member of the large family of leucine-rich
repeat-containing proteins. On the basis of architectural and domain
homology, this gene appears to be a good candidate for secretion in the
extracellular environment and, therefore, may play a role in breast
tissue remodeling and/or epithelium-stroma interactions. Several
interesting genes with a potential role in the regulation of cell cycle
progression were also identified to increase in expression, including
Pescadillo and chaperonin CCT2. Two
putative paracrine/autocrine factors of potential importance in the
regulation of the growth of breast cancer cells were identified to be
highly up-regulated by E2: stanniocalcin 2, a
calcium/phosphate homeostatic hormone; and inhibin-ß B, a
TGF-ß-like factor. Interestingly, we also determined that
E2IG1 and stanniocalcin 2 were
exclusively overexpressed in estrogen-receptor-positive breast cancer
lines, and thus they have the potential to serve as breast cancer
biomarkers. This data provides a comprehensive view of the changes
induced by E2 on the transcriptional program of
human E2-responsive cells, and it also identifies novel and
previously unsuspected gene targets whose expression is affected by
this hormone.
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M. Elkin, I. Cohen, E. Zcharia, A. Orgel, Z. Guatta-Rangini, T. Peretz, I. Vlodavsky, and H. K. Kleinman Regulation of Heparanase Gene Expression by Estrogen in Breast Cancer Cancer Res., December 15, 2003; 63(24): 8821 - 8826. [Abstract] [Full Text] [PDF]
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 Y. Kun, L. C. How, T. P. Hoon, V. B. Bajic, T. S. Lam, A. Aggarwal, H. G. Sze, W. S. Bok, W. C. Yin, and P. Tan Classifying the estrogen receptor status of breast cancers by expression profiles reveals a poor prognosis subpopulation exhibiting high expression of the ERBB2 receptor Hum. Mol. Genet., December 15, 2003; 12(24): 3245 - 3258. [Abstract] [Full Text] [PDF]
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H. E. Cunliffe, M. Ringner, S. Bilke, R. L. Walker, J. M. Cheung, Y. Chen, and P. S. Meltzer The Gene Expression Response of Breast Cancer to Growth Regulators: Patterns and Correlation with Tumor Expression Profiles Cancer Res., November 1, 2003; 63(21): 7158 - 7166. [Abstract] [Full Text] [PDF]
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T. Hayano, M. Yanagida, Y. Yamauchi, T. Shinkawa, T. Isobe, and N. Takahashi Proteomic Analysis of Human Nop56p-associated Pre-ribosomal Ribonucleoprotein Complexes: POSSIBLE LINK BETWEEN Nop56p AND THE NUCLEOLAR PROTEIN TREACLE RESPONSIBLE FOR TREACHER COLLINS SYNDROME J. Biol. Chem., September 5, 2003; 278(36): 34309 - 34319. [Abstract] [Full Text] [PDF]
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S. Oesterreich, W. Deng, S. Jiang, X. Cui, M. Ivanova, R. Schiff, K. Kang, D. L. Hadsell, J. Behrens, and A. V. Lee Estrogen-mediated Down-Regulation of E-cadherin in Breast Cancer Cells Cancer Res., September 1, 2003; 63(17): 5203 - 5208. [Abstract] [Full Text] [PDF]
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L. Pusztai, M. Ayers, J. Stec, E. Clark, K. Hess, D. Stivers, A. Damokosh, N. Sneige, T. A. Buchholz, F. J. Esteva, et al. Gene Expression Profiles Obtained from Fine-Needle Aspirations of Breast Cancer Reliably Identify Routine Prognostic Markers and Reveal Large-Scale Molecular Differences between Estrogen-negative and Estrogen-positive Tumors Clin. Cancer Res., July 1, 2003; 9(7): 2406 - 2415. [Abstract] [Full Text] [PDF]
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N. Yadav, J. Lee, J. Kim, J. Shen, M. C.-T. Hu, C. M. Aldaz, and M. T. Bedford Specific protein methylation defects and gene expression perturbations in coactivator-associated arginine methyltransferase 1-deficient mice PNAS, May 27, 2003; 100(11): 6464 - 6468. [Abstract] [Full Text] [PDF]
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E. K. Lobenhofer, L. Bennett, P. L. Cable, L. Li, P. R. Bushel, and C. A. Afshari Regulation of DNA Replication Fork Genes by 17{beta}-Estradiol Mol. Endocrinol., June 1, 2002; 16(6): 1215 - 1229. [Abstract] [Full Text] [PDF]
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T. Bouras, M. C. Southey, A. C. Chang, R. R. Reddel, D. Willhite, R. Glynne, M. A. Henderson, J. E. Armes, and D. J. Venter Stanniocalcin 2 Is an Estrogen-responsive Gene Coexpressed with the Estrogen Receptor in Human Breast Cancer Cancer Res., March 1, 2002; 62(5): 1289 - 1295. [Abstract] [Full Text] [PDF]
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 K. Ishibashi and M. Imai Prospect of a stanniocalcin endocrine/paracrine system in mammals Am J Physiol Renal Physiol, March 1, 2002; 282(3): F367 - F375. [Abstract] [Full Text] [PDF]
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K. Iwao, R. Matoba, N. Ueno, A. Ando, Y. Miyoshi, K. Matsubara, S. Noguchi, and K. Kato Molecular classification of primary breast tumors possessing distinct prognostic properties Hum. Mol. Genet., January 1, 2002; 11(2): 199 - 206. [Abstract] [Full Text] [PDF]
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 C. A. Iacobuzio-Donahue, B. Ryu, R. H. Hruban, and S. E. Kern Exploring the Host Desmoplastic Response to Pancreatic Carcinoma : Gene Expression of Stromal and Neoplastic Cells at the Site of Primary Invasion Am. J. Pathol., January 1, 2002; 160(1): 91 - 99. [Abstract] [Full Text] [PDF]
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S. Gruvberger, M. Ringner, Y. Chen, S. Panavally, L. H. Saal, A. Borg, M. Ferno, C. Peterson, and P. S. Meltzer Estrogen Receptor Status in Breast Cancer Is Associated with Remarkably Distinct Gene Expression Patterns Cancer Res., August 1, 2001; 61(16): 5979 - 5984. [Abstract] [Full Text] [PDF]
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K. Polyak and G. J. Riggins Gene Discovery Using the Serial Analysis of Gene Expression Technique: Implications for Cancer Research J. Clin. Oncol., June 1, 2001; 19(11): 2948 - 2958. [Abstract] [Full Text] [PDF]
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