Novel Molecular Pathway Mimics Androgen Binding in Advanced Prostate Cancer

Cancer researchers have identified a molecular pathway that explains how advanced prostate tumors that should require androgens for growth manage to survive and spread despite treatment that isolates them from any sex hormone activity.

The outstanding question is whether there is another mechanism that triggers androgen receptor signaling even when there are no sex hormones present.

To answer this question, investigators at the University of North Carolina (Chapel Hill, USA) examined the interaction between androgen receptor regulated genes in prostate cancer cells and coregulatory proteins that included the melanoma antigen gene protein-A11 (MAGE-11).

They reported in the July 9, 2010, issue of the Journal of Biological Chemistry that MAGE-11 contributed to androgen receptor transcriptional activity through an interaction with a protein called p300, a potent and ubiquitous transcriptional regulator. This interaction depended on binding of MAGE-11 to the NH2-terminal domains of the androgen receptor and of p300.

Senior author Dr. Elizabeth M. Wilson, professor of pediatric biochemistry and biophysics at the University of North Carolina, explained, "We found that a small portion of the androgen receptor interacts with the MAGE-11 molecule which serves as a bridge to p300, a strong histone modifying enzyme that increases androgen receptor activity. This is exciting because it shows how the cancer cells have developed a way to boost androgen receptor activity, even in the absence or at low levels of the hormone that binds the androgen receptor. The MAGE-11 molecule is a promising target for shutting down androgen receptor activity that promotes the growth of cancer cells.”

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