TY - JOUR
T1 - Distinct altered patterns of p27(KIP1) gene expression in benign prostatic hyperplasia and prostatic carcinoma
AU - Cordon-Cardo, Carlos
AU - Koff, Andrew
AU - Drobnjak, Marija
AU - Capodieci, Paola
AU - Osman, Iman
AU - Millard, S. Sean
AU - Gaudin, Paul B.
AU - Fazzari, Melissa
AU - Zhang, Zuo Feng
AU - Massague, Joan
AU - Scher, Howard I.
N1 - Funding Information:
Supported in part by Public Health Service (PHS) grants CA-DK47650 (C. Cordon-Cardo) from the National Cancer Institute (NCI) and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (NIH), Department of Health and Human Services; by PHS grants CA68425 (NCI) and GM52597 (National Institute of General Medical Sciences, NIH) (A. Koff); by PHS grant ES06718 (National Institute of Environment Health Sciences, NIH) (Z.-F. Zhang); and by the PepsiCo Foundation (M. Drob-njak and H. I. Scher). A. Koff is also supported by a Pew Scholarship in Biomedical Sciences and the Frederick R. Alder Chair for Junior Faculty. I. Osman is a Molecular Pathology Fellow recipient of a Fellowship from NCI Training Program CA60376. J. Massague is an investigator of the Howard Hughes Medical Institute.
PY - 1998/9/2
Y1 - 1998/9/2
N2 - Background: The p27(KIP1) gene, whose protein product is a negative rgulator 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 p27(KIP1) gene expression in patients with benign prostatic hyperplasia (BPH) and patients with prostate cancer. Methods: We analyzed 130 prostate carcinomas from primary and metastatic site, 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 p27(KIP1) 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 p27(Kip1) 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 p27(KIP1) mRNA in both epithelial cells and stromal cells. However, p27 protein and p27(KIP1) mRNA were almost undetectable in epithelial cells and stromal cells of BPH lesions. Furthermore, p27(Kip1) null mice developed enlarged (hyperplastic) prostate glands. In contrast to BPH, prostate carcinomas were found to contain abundant p27(KIP1) 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 p27(Kip1) expression in the human prostate may be causally linked to BPH and that BPH is not a precursor to prostate cancer.
AB - Background: The p27(KIP1) gene, whose protein product is a negative rgulator 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 p27(KIP1) gene expression in patients with benign prostatic hyperplasia (BPH) and patients with prostate cancer. Methods: We analyzed 130 prostate carcinomas from primary and metastatic site, 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 p27(KIP1) 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 p27(Kip1) 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 p27(KIP1) mRNA in both epithelial cells and stromal cells. However, p27 protein and p27(KIP1) mRNA were almost undetectable in epithelial cells and stromal cells of BPH lesions. Furthermore, p27(Kip1) null mice developed enlarged (hyperplastic) prostate glands. In contrast to BPH, prostate carcinomas were found to contain abundant p27(KIP1) 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 p27(Kip1) expression in the human prostate may be causally linked to BPH and that BPH is not a precursor to prostate cancer.
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U2 - 10.1093/jnci/90.17.1284
DO - 10.1093/jnci/90.17.1284
M3 - Article
C2 - 9731735
AN - SCOPUS:0032475438
SN - 0027-8874
VL - 90
SP - 1284
EP - 1291
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 17
ER -
