Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma

Cordon-Cardo, Carlos, Koff, Andrew, Drobnjak, Marija, Capodieci, Paola, Osman, Iman, Millard, S. Sean, Gaudin, Paul B., Fazzari, Melissa, Zhang, Zuo-Feng, Massague, Joan and Scher, Howard I. (1998) Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma. JNCI: Journal of the National Cancer Institute, 90 17: 1284-1291. doi:10.1093/jnci/90.17.1284


Author Cordon-Cardo, Carlos
Koff, Andrew
Drobnjak, Marija
Capodieci, Paola
Osman, Iman
Millard, S. Sean
Gaudin, Paul B.
Fazzari, Melissa
Zhang, Zuo-Feng
Massague, Joan
Scher, Howard I.
Title Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma
Formatted title
Distinct altered patterns of p27KIP1 gene expression in benign prostatic hyperplasia and prostatic carcinoma
Journal name JNCI: Journal of the National Cancer Institute   Check publisher's open access policy
ISSN 1460-2105
0027-8874
Publication date 1998-09-02
Sub-type Article (original research)
DOI 10.1093/jnci/90.17.1284
Open Access Status Not Open Access
Volume 90
Issue 17
Start page 1284
End page 1291
Total pages 8
Place of publication Bethesda, MD, United States
Publisher U.S. National Cancer Institute
Language eng
Formatted abstract
Background: The p27KIP1 gene, whose protein product is a negative regulator of the cell cycle, is a potential tumor suppressor gene; however, no tumor-specific mutations of this gene have been found in humans. This study was undertaken to identify and to assess potential alterations of p27KIP1 gene expression in patients with benign prostatic hyperplasia (BPH) and patients with prostate cancer. Methods: We analyzed 130 prostate carcinomas from primary and metastatic sites, as well as prostate samples from normal subjects and from patients with BPH. Immunohistochemistry and in situ hybridization were used to determine the levels of expression and the microanatomical localization of p27 protein and messenger RNA (mRNA), respectively. Immunoblotting and immunodepletion assays were performed on a subset of the prostate tumors. Associations between alterations in p27KIP1 expression and clinicopathologic variables were evaluated with a nonparametric test. The Kaplan-Meier method and the logrank test were used to compare disease-relapse-free survival. Prostate tissues of p27KIP1 null (i.e., knock-out) and wild-type mice were also evaluated. Results: Normal human prostate tissue exhibited abundant amounts of p27 protein and high levels of p27KIP1 mRNA in both epithelial cells and stromal cells. However, p27 protein and p27KIP1 mRNA were almost undetectable in epithelial cells and stromal cells of BPH lesions. Furthermore, p27KIP1 null mice developed enlarged (hyperplastic) prostate glands. In contrast to BPH, prostate carcinomas were found to contain abundant p27KIP1 mRNA but either high or low to undetectable levels of p27 protein. Primary prostate carcinomas expressing lower levels of p27 protein appeared to be biologically more aggressive (two-sided P = .019 [Cox regression analysis]). Conclusions/Implications: On the basis of these results, we infer that loss of p27KIP1 expression in the human prostate may be causally linked to BPH and that BPH is not a precursor to prostate cancer.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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