[HTML][HTML] Estrogen receptor-α mediates gene expression changes and growth response in ovarian cancer cells exposed to estrogen

AJM O'Donnell, KG Macleod, DJ Burns… - Endocrine-related …, 2005 - erc.bioscientifica.com
AJM O'Donnell, KG Macleod, DJ Burns, JF Smyth, SP Langdon
Endocrine-related cancer, 2005erc.bioscientifica.com
Estrogens play a significant role in the development, growth, invasion and metastasis of
ovarian tumors. The transcriptional program regulated by 17β-estradiol (E 2) in human
ovarian cancer cell lines was analyzed using cDNA microarrays containing 1200 cancer-
related genes. Twenty-eight transcripts had at least a threefold change in expression in E 2-
treated PEO1 ovarian carcinoma cells compared with controls. These differences were
confirmed by real-time quantitative PCR and shown to be dependent upon the expression of …
Estrogens play a significant role in the development, growth, invasion and metastasis of ovarian tumors. The transcriptional program regulated by 17β-estradiol (E 2 ) in human ovarian cancer cell lines was analyzed using cDNA microarrays containing 1200 cancer-related genes. Twenty-eight transcripts had at least a threefold change in expression in E 2 -treated PEO1 ovarian carcinoma cells compared with controls. These differences were confirmed by real-time quantitative PCR and shown to be dependent upon the expression of functional estrogen receptor-α (ERα). Consistent with this, these gene expression changes were blocked by the anti-estrogen tamoxifen. The use of ERα- and ERβ-specific ligands allowed molecular dissection of the E 2 response and showed that ERα activation was responsible for the observed changes in gene expression, whereas ERβ played no significant role. Inhibition of de novo protein synthesis by cycloheximide was used to distinguish between primary and secondary target genes regulated by E 2 . Actinomycin D was used to show that changes in gene expression levels induced by E 2 were a result of changes in transcription and not due to changes in mRNA stability. The results presented here demonstrate that estrogen-driven growth of epithelial ovarian carcinoma is mediated by activation of ERα-mediated, and not ERβ-mediated, transcription.
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