Accession Number:

ADA446355

Title:

Investigating the Role of p57Kip2 in Prostate Cancer

Descriptive Note:

Annual summary 1 Sep 2004-31 Aug 2005

Corporate Author:

VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN

Personal Author(s):

Report Date:

2005-09-01

Pagination or Media Count:

9.0

Abstract:

The aim of this project is to characterize the functional significance of p57Kip2, one of Cyclin-dependent kinases inhibitors CKI of the INK4 family, in prostate proliferation, differentiation, tumorigenesis, and progression. In the present study, we have investigated the expression of P57Kip2 in human prostate cancer cases by immunohistochemistry. The average p57Kip2 labeling index in noncancerous lesions was 47.47. However, the labeling index significantly decreased pO.OOl in PIN 10.21 and carcinoma 2.85 lesions. When virus- mediated overexpression of p57Kip2 in prostate cancer cells LNCaP, significantly suppressed the cells motility, potential for invasion, arrested the cell cycles at GOG1 stage, and induced apoptosis. Furthermore, when the LNCaP cells stable transfected by p57Kip2expression vector were recombined with rat urogenital mesenchyme rUGM and subsecuently grafted into a male athymic mouse host using tissue recombinant technioues, the LNCaP tumors transformed into well differentiated squamous tumors and showed increased keratin synthesis or no tumor formation in athymic mice. These results suggest that decreased expression of p57Kip2 occurs frequently in human prostate cancer even early in PIN lesion and p57Kip2 overexpression contributes to the downregulation of cell proliferation. Thus, p57Kip2 is an important gene in prostate cancer tumorigenesis and progression.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE