Journal
CELL DEATH & DISEASE
Volume 4, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/cddis.2013.235
Keywords
breast cancer; androgen receptor; DAX-1; aromatase
Categories
Funding
- Progetti di Ricerca di Interesse Nazionale (PRIN)-Ministero Istruzione Universita e Ricerca (MIUR) [20085Y7XT5]
- Associazione Italiana Ricerca sul Cancro (AIRC) [11595]
- Reintegration AIRC/Marie Curie International Fellowship in Cancer Research
Ask authors/readers for more resources
Sexual hormones, estrogens and androgens, determine biological response in a tissue-and gender-specific manner and have a pivotal role in endocrine-mediated tumorigenesis. In situ estrogen production by aromatase is a critical determinant for breast cancer growth and progression. On the contrary, clinical and in vitro studies indicate that androgens have a protective role in mammary carcinogenesis. Here, we demonstrated, in hormone-dependent breast cancer cells, the existence of a functional interplay between the androgen receptor (AR), the orphan nuclear receptor DAX-1 and the aromatase enzyme involved in the inhibition of the estrogen-dependent breast cancer cell proliferation exerted by androgen signaling. Indeed, our results revealed, in MCF-7 cells, that ligand-activated AR induces the expression of the orphan nuclear receptor DAX-1 by direct binding to a newly identified androgen-response-element within the DAX-1 proximal promoter. In turn, androgen-induced DAX-1 is recruited, in association with the corepressor N-CoR, within the SF-1/LRH-1 containing region of the aromatase promoter, thereby repressing aromatase expression and activity. In elucidating a novel mechanism by which androgens, through DAX-1, inhibit aromatase expression in breast cancer cell lines, these findings reinforce the theory of androgen-opposing estrogen-action, opening new avenues for therapeutic intervention in estrogen-dependent breast tumors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available