Hepsin cooperates with MYC in the progression of adenocarcinoma in a prostate cancer mouse model.

Abstract

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.

• Authors: Srinivas Nandana, Katharine Ellwood-Yen, Charles Sawyers, Marcia Wills, Brandy Weidow, Thomas Case, Valeri Vasioukhin, Robert Matusik
• Journal: The Prostate (Prostate) Vol. 70 Issue 6 Pg. 591-600 (May 01 2010) ISSN: 1097-0045 [Electronic] United States
• PMID: 19938013 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Androgen-Binding Protein
• Proto-Oncogene Proteins c-myc
• probasin
• Serine Endopeptidases
• hepsin

Topics

• Adenocarcinoma (metabolism, pathology)
• Androgen-Binding Protein (genetics, metabolism)
• Animals
• Disease Models, Animal
• Disease Progression
• Male
• Mice
• Mice, Transgenic
• Prostatic Neoplasms (metabolism, pathology)
• Proto-Oncogene Proteins c-myc (genetics, metabolism)
• Serine Endopeptidases (genetics, metabolism)
• Time Factors