Genomic analyses of breast cancer cells: 17-hydroxysteroid dehydrogenase type 1 induces transcriptional changes in estradiol-dependent and independent manners

17-HSD1 expression modulates T47D transcript profile in in steroid-deprived medium. The enzyme specifically regulates apoptosis and cancer-related genes in T47D cells cultured in steroid-deprived medium. Genes that primarily involved in Cell cycle progression, such as the Cyclin A2 gene, CCNA2, are generally down-regulated whereas most genes involved in apoptosis and cell death, such as the proapoptotic gene XAF1 and FGF12, are on the contrary up-regulated by 17-HSD1 knockdown, and 21% of the modulated genes belong to this latter functional category. This correborates with its role previously shown in increasing breast cancer cell proliferation (Aka et al, 2010) and indicates that in addition to its direct role as cell proliferation via incresing E2 and decreasing DHT, 17-HSD1 may also be involved in oncogenesis by favoring its anti-apoptosis pathway in breast cancer cells 17-HSD1 may also be involved in oncogenesis by favoring anti-apoptosis pathway and/or inhibiting cell survival pathway. We tested the ability of estrogen to induce or repress endogenous genes of T47D by microarray analysis. A total of 131 genes were found to increase or decrease 1.5-fold or higher in response to 17 beta-estradiol (1 nM for 48 h). Besides, the gene regulation occuring in steroid-deprived conditions showed that 17-HSD1 modulates gene expression in steroid-independent manners. Our study thus demonstrates that 17-HSD1 modulates the E2-independent transcription of endogenous genes in T47D cells. The E2-dependent transcription as well as the E2-independent transcription are significantly modulated by 17-HSD1 in breast cancer cells We first report here that breast cancer cell transcript profile is independtly modulated by both 17-HSD1 and its principale product estradiol.

8

Aka JA, Calvo EL, Lin SX