Overexpression of telomerase-associated chaperone proteins in prostatic intraepithelial neoplasia and carcinomas

Over 90% of prostate cancers express telomerase activity. In an experimental model, hsp90 and p23, which are necessary for telomerase assembly and function, dramatically increase during tumorigenic conversion. We immunohistochemically analyzed 60 prostate carcinomas, 50 prostatic intraepithelial neo...

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Bibliographic Details
Published in:	Oncology reports Vol. 20; no. 3; pp. 613 - 617
Main Authors:	ELMORE, Lynne W, FORSYTHE, Robert, FORSYTHE, Heidi, BRIGHT, A. Taylor, NASIM, Suhail, ENDO, Kanendori, HOLT, Shawn E
Format:	Journal Article
Language:	English
Published:	Athens S.n. 01-09-2008
Subjects:	Adenocarcinoma - metabolism Adenocarcinoma - secondary Aged Aged, 80 and over Biological and medical sciences Cell Nucleus - metabolism HSP90 Heat-Shock Proteins - metabolism Humans Immunoenzyme Techniques Intramolecular Oxidoreductases - metabolism Male Medical sciences Middle Aged Neoplasm Staging Nephrology. Urinary tract diseases Prognosis Prostaglandin-E Synthases Prostate - metabolism Prostate - pathology Prostatic Hyperplasia - metabolism Prostatic Hyperplasia - pathology Prostatic Intraepithelial Neoplasia - metabolism Prostatic Intraepithelial Neoplasia - pathology Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Telomerase - metabolism Tumors Tumors of the urinary system Urinary tract. Prostate gland Catalytic subunit Premalignant lesion Urinary system disease Prostate disease Enzyme Chaperone Gene overexpression Prostate intraepithelial neoplasia Malignant tumor p23 prostatic intraepithelial neoplasia Cancerology hsp90 Heat shock protein hTERT Male genital diseases Prostate cancer Telomerase chaperones Cancer Heat shock protein 90
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Summary:	Over 90% of prostate cancers express telomerase activity. In an experimental model, hsp90 and p23, which are necessary for telomerase assembly and function, dramatically increase during tumorigenic conversion. We immunohistochemically analyzed 60 prostate carcinomas, 50 prostatic intraepithelial neoplasias (PIN) and 25 benign prostatic tissues to determine whether hsp90/p23 expression correlates with advancing stage and whether chaperone distribution overlaps with hTERT, the catalytic component of telomerase. Strong expression of hsp90/p23 was detected in approximately 95% of PIN and carcinomas without relationship to Gleason score. While hsp90/p23 immunostaining was predominantly diffuse and cytoplasmic, nuclear immunoreactivity was observed in several moderate-to-high grade carcinomas, and those carcinomas with nuclear chaperone staining exhibited detectable hTERT. Our data suggest enhanced chaperone-mediated telomerase assembly as a mechanism for increased activity in advanced prostate carcinomas, stable association between chaperones and telomerase in vivo, and utility for chaperone immunostaining to identify focal PIN in the context of widespread hyperplasia.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1021-335X 1791-2431
DOI:	10.3892/or_00000049