INDIGO Home University of Illinois at Urbana-Champaign logo uic building uic pavilion uic student center

p27(Kip1) deficiency promotes prostate carcinogenesis but does not affect the efficacy of retinoids in suppressing the neoplastic process

Show simple item record

Bookmark or cite this item: http://hdl.handle.net/10027/7741

Files in this item

File Description Format
PDF 1471-2407-10-541.pdf (1MB) (no description provided) PDF
Title: p27(Kip1) deficiency promotes prostate carcinogenesis but does not affect the efficacy of retinoids in suppressing the neoplastic process
Author(s): Taylor, Winna; Mathias, Amanda; Ali, Arshia; Ke, Hengning; Stoynev, Nikolay; Shilkaitis, Anne; Green, Albert; Kiyokawa, Hiroaki; Christov, Konstantin
Subject(s): p27Kip1 prostate cell proliferation
Abstract: Background: p27 is a cell cycle suppressor gene, whose protein is a negative regulator of cyclin/cdk complexes. p27 is also a potential target of retinoids in cancer prevention studies. In benign prostate hyperplasia (BPH), and in most carcinomas, p27Kip1 is down-regulated, suggesting its potential resistance to retinoids. To test this hypothesis, we examined the efficacy of 9-cis retinoic acid (9cRA) to suppress prostate cell proliferation (PECP) and carcinogenesis in p27Kip1 deficient mice. Methods: p27Kip1 deficient (-/-), heterozygous (+/-) and homozygous (+/+) mice were treated for 7 days with testosterone, 9cRA, or with both, and cell proliferation in dorsolateral prostate (DLP) was determined by BrdU labeling. Prostate carcinogenesis was induced by N-Methyl-N-Nitrosourea (MNU) and hormone stimulation. Results: PECP in DLP of two-month-old mice of all genotypes was similar but significantly increased in old p27-/- mice only. Testosterone treatment increased PECP in all three p27 genotypes with the highest values in p27-/- mice. p27Kip1 deficiency did not affect the response of PEC to 9cRA and to 9cRA+testosterone. The decrease of p27Kip1 in p27+/- and p27-/- mice progressively increased the incidence and frequency of PIN and tumors. 9cRA suppressed PIN in all three p27 genotypes and this was associated with decreased PECP and increased cellular senescence. Conclusions: This data indicates that p27Kip1 deficiency promotes prostate cell proliferation and carcinogenesis but does not affect 9cRA’s potential to suppress prostate carcinogenesis, suggesting that patients with PIN and carcinomas lacking or having a low level of p27Kip1 expression may also benefit from clinical trials with retinoids.
Issue Date: 2010-10-08
Publisher: BioMed Central
Citation Info: Taylor, W., Mathias, A., Ali, A., Ke, H., Stoynev, N., Shilkaitis, A., Green, A., Kiyokawa, H., & Christov, K. 2010. p27Kip1 deficiency promotes prostate carcinogenesis but does not affect the efficacy of retinoids in suppressing the neoplastic process. BMC Cancer, 10: 541. DOI: 10.1186/1471-2407-10-541
Type: Article
Description: © 2010 Taylor et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The original source is available through BioMed Central at DOI: 10.1186/1471-2407-10-541.
URI: http://hdl.handle.net/10027/7741
ISSN: 1471-2407
Sponsor: This study was supported by CA095712 and CN-35112 from NIH.
Date Available in INDIGO: 2011-05-27
 

This item appears in the following Collection(s)

Show simple item record

Statistics

Country Code Views
United States of America 151
China 46
Germany 7
United Kingdom 6
Denmark 4

Browse

My Account

Information

Access Key