Department of Molecular, Cell and Cancer Biology; Program in Molecular Medicine
Cancer Biology | Cell Biology | Cells | Hormones, Hormone Substitutes, and Hormone Antagonists
The role of ERbeta in prostate cancer is unclear, although loss of ERbeta is associated with aggressive disease. Given that mice deficient in ERbeta do not develop prostate cancer, we hypothesized that ERbeta loss occurs as a consequence of tumorigenesis caused by other oncogenic mechanisms and that its loss is necessary for tumorigenesis. In support of this hypothesis, we found that ERbeta is targeted for repression in prostate cancer caused by PTEN deletion and that loss of ERbeta is important for tumor formation. ERbeta transcription is repressed by BMI-1, which is induced by PTEN deletion and important for prostate tumorigenesis. This finding provides a mechanism for how ERbeta expression is regulated in prostate cancer. Repression of ERbeta contributes to tumorigenesis because it enables HIF-1/VEGF signaling that sustains BMI-1 expression. These data reveal a positive feedback loop that is activated in response to PTEN loss and sustains BMI-1.
DOI of Published Version
Cell Rep. 2015 Mar 31;10(12):1982-91. doi: 10.1016/j.celrep.2015.02.063. Epub 2015 Mar 26. Link to article on publisher's site
Mak P, Li J, Samanta S, Chang C, Jerry D, Davis RJ, Leav I, Mercurio AM. (2015). Prostate Tumorigenesis Induced by PTEN Deletion Involves Estrogen Receptor beta Repression. Molecular, Cell and Cancer Biology Publications. https://doi.org/10.1016/j.celrep.2015.02.063. Retrieved from https://escholarship.umassmed.edu/mccb_pubs/5
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