Using a Novel Transgenic Mouse Model to Study c-Myc Oncogenic Pathway in Castration Resistance and Chemoresistance of Prostate Cancer
Annual rept. 15 Sep 2013 - 14 Sep 2014
BAYLOR COLL OF MEDICINE HOUSTON TX
Pagination or Media Count:
We previously generated a PB-Cre4CAG-SMIL transgenic model allowing Cre-induced expression of c-Myc oncogene and Luc2 for BLI imaging in vivo in prostate epithelia. Once turned on, c-Myc and Luc2 expression will not rely on androgen, which allows studying castration response and CRPC. However, most Cre4CAG-SMIL mice did not develop invasive prostate tumors up to 2-year of age, potentially due to c-Myc induced p53 activation. Hence, we proposed to generate PB-Cre4CAG-SMILp53loxPloxP mice to conditionally knock out p53 and turn on c-Myc expression in prostate for rapid onset of PCa, and use this model to study CRPC and chemoresistance of CRPC. In the initial year, we have carried out all the proposed studies as described in SOW on schedule, including performing extensive multi-rounds of crossing to generate the target PB-Cre4CAG-SMILp53loxPloxP mice, and the initial characterization of prostate histopathology to confirm early onset of mPIN in 8-week old PB-Cre4CAG-SMIL p53loxPloxP mice. We have also identified a potential technical problem and provided alternative approaches to address it.
- Medicine and Medical Research