Effect of estrogen and eNOS activity on cancer associated lncRNA expression in hormone-dependent cancers

Breast cancer and prostate cancer (PCa) are the most common invasive cancers in women and men, respectively. Although these cancers arise in organs that are different for anatomy and physiological function, either breast and prostate cancers are typically hormone-dependent and have remarkable biological similarities. They are hormonally fuelled cancers driven by the sex steroid hormones, estrogen and androgen, that activate their respective nuclear estrogen receptor (ER ?/?) or androgen receptor (AR). Moreover, these nuclear receptors interact with a plethora of other transcription factors and co-factors, like the endothelial nitric oxide synthase (eNOS) known to mark the most adverse phenotype in PCa microenvironment, which aid ER and AR to elicit a pro-tumorigenic gene expression program. Recent studies revealed that lncRNAs represent the leading edge of cancer research. Their identity, function and deregulation in cancer are only beginning to be understood, and recent data suggest that they may serve as master drivers of carcinogenesis. In this study, the expression of different hormone receptors and eNOS was evaluated in several breast and prostate cell lines, and cell lines classified in different groups based on different expression pattern. Then, the level of a subset of cancer associated lncRNA (e.g MALAT1, HOTAIR, GAS5) was quantified by real time PCR in each cell line, before and after estrogen treatment. In addition, the effect of selective inhibitor of NOS, like L-NAME or 7N, and the hypoxia was also evaluated in the regulation of lncRNA expression. This results allowed us to better understand how the same condition can lead to different responses in breast and prostate cancer cell lines with different hormone receptor expression profile and/or level of eNOS.