Hepsin cooperates with MYC in the progression of adenocarcinoma in a prostate cancer mouse model.
BACKGROUND
Hepsin is a cell surface protease that is over-expressed in more than 90% of human prostate cancer cases. The previously developed Probasin-hepsin/Large Probasin-T antigen (PB-hepsin/LPB-Tag) bigenic mouse model of prostate cancer demonstrates that hepsin promotes primary tumors that are a mixture of adenocarcinoma and neuroendocrine (NE) lesions, and metastases that are NE in nature. However, since the majority of human prostate tumors are adenocarcinomas, the contribution of hepsin in the progression of adenocarcinoma requires further investigation.


METHODS
We crossed the PB-hepsin mice with PB-Hi-myc transgenic mouse model of prostate adenocarcinoma and characterized the tumor progression in the resulting PB-hepsin/PB-Hi-myc bigenic mice.


RESULTS
We report that PB-hepsin/PB-Hi-myc bigenic mice develop invasive adenocarcinoma at 4.5 months. Further, histological analysis of the 12- to 17-month-old mice revealed that the PB-hepsin/PB-Hi-myc model develops a higher grade adenocarcinoma compared with age-matched tumors expressing only PB-Hi-myc. Consistent with targeting hepsin to the prostate, the PB-hepsin/PB-Hi-myc tumors showed higher hepsin expression as compared to the age-matched myc tumors. Furthermore, endogenous expression of hepsin increased in the PB-Hi-myc mice as the tumors progressed.


CONCLUSIONS
Although we did not detect any metastases from the prostates in either the PB-hepsin/PB-Hi-myc or the PB-Hi-myc mice, our data suggests that hepsin and myc cooperate during the progression to high-grade prostatic adenocarcinoma.
Nandana
Srinivas
S
Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2765, USA.
Ellwood-Yen
Katharine
K
Sawyers
Charles
C
Wills
Marcia
M
Weidow
Brandy
B
Case
Thomas
T
Vasioukhin
Valeri
V
Matusik
Robert
R
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D000727:Androgen-Binding Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
D000727:Androgen-Binding Protein; D016271:Proto-Oncogene Proteins c-myc; C027519:probasin; D012697:Serine Endopeptidases; C055645:hepsin