Concordant induction of 15-lipoxygenase-1 and mutant p53 expression in human prostate adenocarcinoma: Correlation with Gleason staging

Uddhav P. Kelavkar, Cynthia Cohen, Hideki Kamitani, Thomas E. Eling, Kamal F. Badr

Research output: Contribution to journalArticle

Abstract

We recently reported that the mutant form of the tumor-suppressor gene p53 up-regulates 15-LO-1 gene expression in a murine cell line. Here, we examine the expression of 15-lipoxygenase (LO)-1 and mutant p53 (mtp53) in human prostatic tissues and 15-LO-1 in the human prostate adenocarcinoma cell line PC-3. Reverse transcription-PCR and western analyses conclusively demonstrated expression of 15-LO-1 in PC-3 cells. Western blotting for 15-LO-1 in freshly resected 'normal' and prostate adenocarcinoma specimens showed 15-LO-1 expression in normal tissue, but significantly higher levels were detected in prostate adenocarcinomas. Prostate adenocarcinoma tissues generated chirally pure 13-S-hydroxyoctadecadienoic acid from exogenous linoleic acid, a preferred substrate of 15-LO-1. To study the correlation of 15-LO-1 expression with mtp53 in prostate cancer, we immunostained 48 prostatectomy specimens obtained by transurethral resection of the prostate and needle biopsy (median age 68 years, range 52-93) of different Gleason grades (n = 48), using antibodies specific for 15-LO-1, mtp53 and MIB-1 (a proliferation marker). We compared staining in cancerous foci with adjacent normal appearing prostate tissues. In only 5 of 48 patients did 'normal' tissue adjacent to cancerous foci display staining for 15-LO-1. However, no staining for mtp53 was observed in any of the normal tissues. In cancer foci, robust staining was observed for both 15-LO-1 (36 of 48, 75%) and mtp53 (19 of 48, 39%). Furthermore, the intensities of expression of 15-LO-1 and mtp53 correlated positively with each other (P

Original languageEnglish (US)
Pages (from-to)1777-1787
Number of pages11
JournalCarcinogenesis
Volume21
Issue number10
StatePublished - 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research

Cite this

Kelavkar, U. P., Cohen, C., Kamitani, H., Eling, T. E., & Badr, K. F. (2000). Concordant induction of 15-lipoxygenase-1 and mutant p53 expression in human prostate adenocarcinoma: Correlation with Gleason staging. Carcinogenesis, 21(10), 1777-1787.