Investigating the Role of p57Kip2 in Prostate Cancer

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...

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Bibliographic Details
Main Author: Jin, Ren J
Format: Report
Language:English
Subjects:
CELLS(BIOLOGY)
CYCLES
GENETIC TISSUE IDENTIFICATION
HISTOCHEMISTRY
HUMANS
IMMUNOCHEMISTRY
LESIONS
Medicine and Medical Research
NEOPLASMS
PHOSPHORUS TRANSFERASES
PRODUCTION
PROSTATE CANCER
THYMUS
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Summary: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 GO/G1 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.