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 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.
Elmore
Lynne W
LW
Department of Pathology, Virginia Commonwealth University, 1101 East Marshall Street, Richmond, VA 23298-0662, USA.
Forsythe
Robert
R
Forsythe
Heidi
H
Bright
A Taylor
AT
Nasim
Suhail
S
Endo
Kanendori
K
Holt
Shawn E
SE
D000230:Adenocarcinoma / Q000378:metabolism / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D000071876:Prostaglandin-E Synthases; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D019098:Telomerase / Q000378:metabolism*
D018841:HSP90 Heat-Shock Proteins; C509186:TERT protein, human; D019098:Telomerase; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases