Accession Number : ADA551776


Title :   Interactions Between IGFBP-3 and Nuclear Receptors in Prostate Cancer Apoptosis


Descriptive Note : Final rept. 15 Dec 2006-14 Dec 2009


Corporate Author : CALIFORNIA UNIV LOS ANGELES


Personal Author(s) : Lee, Kuk-Wha


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a551776.pdf


Report Date : Jan 2010


Pagination or Media Count : 50


Abstract : IGFBP 3 is a potent inducer of apoptosis in both androgen-dependent and androgen-independent prostate cancer lines. When the nuclear receptor RXRalpha was described as an unexpected intracellular binding partner for IGFBP-3 and effects on DNA transcription were demonstrated, rapid effects of IGFBP-3 on programmed cell death (apoptosis) still could not be explained These rapid effects on apoptosis were clarified when I hypothesized that IGFBP 3 was a biological signal for Nur77 nuclear receptor translocation to the mitochondria where an apoptotic cascade is initiated. We proposed to determine scientifically the protein regions in each of these important cell death molecules that essential for apoptotic action and demonstrate this observation with mouse models. Our data so far reveal a nuclear export sequence in IGFBP-3. Mutation of this sequence impairs its apoptotic activity. Utilizing the IGFBP 3 KO mouse, we show that IGFBP-3 s critical role in castration induced apoptosis. Mating studies are underway to determine the effects of genetically deleting Nur77 and IGFBP-3 in the ontogeny of prostate cancer.


Descriptors :   *APOPTOSIS , *PROSTATE CANCER , ANDROGENS , MUTATIONS , NUCLEAR MEDICINE , RECEPTOR SITES(PHYSIOLOGY)


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE