Accession Number : ADA569753


Title :   The Role of Retinal Determination Gene Network (RDGN) in Hormone Signaling Transduction and Prostate Tumorigenesis


Descriptive Note : Annual rept. 30 Sep 2011-29 Sep 2012


Corporate Author : JEFFERSON MEDICAL COLL PHILADELPHIA PA


Personal Author(s) : Wu, Kongming


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a569753.pdf


Report Date : Oct 2012


Pagination or Media Count : 18


Abstract : The recurrence of prostate cancer is mainly due to the transition of initially androgen-dependent cellular proliferation to androgen-independent growth, or castration-resistant prostate cancers (CRPC). To improve the current therapeutic efficiencies, understanding the mechanisms is critical for developing novel strategies. We found that cell fate determine factor DACH1 regulated AR signaling and androgen-dependent growth. We hypothesis that DACH1/Six1/Eya pathway is an endogenous regulator of AR trans-activation and contributes to prostate tumor onset and progression. New studies demonstrated that DACH1 inhibited the prostate cancer cellular proliferation, not only on AR positive and androgenindependent C4-2 cells but also on AR negative PC-3 and 22RV1 cells. DACH1 inhibited in vitro cellular migration, invasion and tumor growth of PC-3 cells. mRNA microarray analyses and functional validation indicate that repression of IL-6 signaling by DACH1 may be a key molecular mechanism. Inhibitory function of Eya1 on AR transactivation required a phosphates activity and could be enhanced by ectopic expression of co-repressors. Together, our studies show that conserved DACH/Six/Eya pathway regulates hormone signaling and prostate cellular growth. The results may provide a new mechanism for controlling AR signaling transduction and prostate tumorigenesis.


Descriptors :   *GENES , *HORMONES , *PROSTATE CANCER , ANDROGENS , CELLS(BIOLOGY) , FUNCTIONS , GROWTH(PHYSIOLOGY) , HYPOTHESES , INHIBITION , MOLECULES , PROSTATE GLAND , TRANSDUCERS , TRANSITIONS


Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE