TY - JOUR
T1 - Cancer resistance in transgenic mice expressing the SAC module of Par-4
AU - Zhao, Yanming
AU - Burikhanov, Ravshan
AU - Qiu, Shirley
AU - Lele, Subodh M.
AU - Jennings, C. Darrell
AU - Bondada, Subbarao
AU - Spear, Brett
AU - Rangnekar, Vivek M.
PY - 2007/10/1
Y1 - 2007/10/1
N2 - Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal/immortalized cells. The cancer-specific proapoptotic action of Par-4 is encoded in its centrally located SAC domain. We report here the characterization of a novel mouse model with ubiquitous expression of the SAC domain. Although SAC transgenic mice displayed normal development and life span, they were resistant to the growth of spontaneous, as well as oncogene-induced, autochthonous tumors. Resistance to tumorigenesis was linked to inhibition of nuclear factor-κB activity and induction of apoptosis by the SAC domain. Collectively, our findings provide genetic evidence that the SAC domain of Par-4 confers cancer resistance in transgenic mice without compromising normal viability or aging, and may have therapeutic significance.
AB - Prostate apoptosis response-4 (Par-4) is a tumor-suppressor protein that induces apoptosis in cancer cells, but not in normal/immortalized cells. The cancer-specific proapoptotic action of Par-4 is encoded in its centrally located SAC domain. We report here the characterization of a novel mouse model with ubiquitous expression of the SAC domain. Although SAC transgenic mice displayed normal development and life span, they were resistant to the growth of spontaneous, as well as oncogene-induced, autochthonous tumors. Resistance to tumorigenesis was linked to inhibition of nuclear factor-κB activity and induction of apoptosis by the SAC domain. Collectively, our findings provide genetic evidence that the SAC domain of Par-4 confers cancer resistance in transgenic mice without compromising normal viability or aging, and may have therapeutic significance.
UR - http://www.scopus.com/inward/record.url?scp=35148859307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35148859307&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-2124
DO - 10.1158/0008-5472.CAN-07-2124
M3 - Article
C2 - 17909035
AN - SCOPUS:35148859307
SN - 0008-5472
VL - 67
SP - 9276
EP - 9285
JO - Cancer Research
JF - Cancer Research
IS - 19
ER -