The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenesis
Annual rept. 30 Sep 2012-29 Sep 2013
JEFFERSON MEDICAL COLL PHILADELPHIA PA
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Prostate cancer is the most frequent malignancy and the second leading cause of cancer-related death among men in the United States. Based on the unique characteristics that those prostate epithelia are dependent on androgen for growth and survival, androgen deprivation therapy ADT has been a first choice of prostate cancer treatment. Despite early success to suppress prostate tumor growth, ADT eventually fails leading to recurrent tumor growth in a hormone-refractory manner, even though AR remains to function in hormone-refractory prostate cancer. We identified a member of androgen receptor AR co-regulator, named dachshund dac. dac was originally discovered as a dominant inhibitor of hyperactive growth factor receptors in genetic screens. RDGN pathway, consisting of the dachshund dac, eyes absent eya, eyeless, and sine oculis so Six genes DACH1 is structurally distinct to the current known tumor suppressors. We propose this unique function as a new type of tumor suppressor and refer to DACH1 as a commandeering tumor suppressor. Recently, we reported that expression of DACH1 is lost in human prostate cancer tissues and restoration of DACH1 inhibited ligand induced AR activity. Although the abnormal expressions of RDGN genes have been reported in prostate cancer, the precise role of RDGN in prostate cancer is not clear.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research