Differential expression of cyclooxygenase-2 and its regulation by tumor necrosis factor-α in normal and malignant prostate cells

• Published in: Cancer research (Chicago, Ill.) Ill.), 2001-03, Vol.61 (6), p.2720-2726
• Main Authors: SUBBARAYAN, Vemparala, SABICHI, Anita L, LLANSA, Norma, LIPPMAN, Scott M, MENTER, David G
• Format: Article
• Language: English
• Subjects: Apoptosis - drug effects; Apoptosis - physiology; Biological and medical sciences; Blotting, Northern; Cells, Cultured; Cyclooxygenase 2; Dinoprostone - biosynthesis; Enzyme Induction - drug effects; Fluorescent Antibody Technique; Gene Expression Regulation, Neoplastic - drug effects; Humans; Isoenzymes - biosynthesis; Isoenzymes - genetics; Isoenzymes - metabolism; Male; Medical sciences; Membrane Proteins; Nephrology. Urinary tract diseases; Prostaglandin-Endoperoxide Synthases - biosynthesis; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandin-Endoperoxide Synthases - metabolism; Prostate - drug effects; Prostate - enzymology; Prostatic Neoplasms - enzymology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Subcellular Fractions - drug effects; Subcellular Fractions - enzymology; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - pharmacology; Tumors of the urinary system; Up-Regulation - drug effects; Urinary tract. Prostate gland
• ISSN: 0008-5472; 1538-7445

Cyclooxygenase (COX)-2 expression is elevated in some malignancies; however, information is scarce regarding COX-2 contributions to the development of prostate cancer and its regulation by inflammatory cytokines. The present study compared and contrasted the expression levels and subcellular distribution patterns of COX-1 and COX-2 in normal prostate [prostate epithelial cell (PrEC), prostate smooth muscle (PrSM), and prostate stromal (PrSt)] primary cell cultures and prostatic carcinoma cell lines (PC-3, LNCaP, and DU145). The basal COX-2 mRNA and protein levels were high in normal PrEC and low in tumor cells, unlike many other normal cells and tumor cells. Because COX-2 levels were low in prostate smooth muscle cells, prostate stromal cells, and tumor cells, we also examined whether COX-1 and COX-2 gene expression was elevated in response to tumor necrosis factor-alpha (TNF-alpha), a strong inducer of COX-2 expression. Northern blot analysis and reverse transcription-PCR demonstrated different patterns and kinetics of expression for COX-1 and COX-2 among normal cells and tumor cells in response to TNF-alpha. In particular, COX-2 protein levels increased, and the subcellular distribution formed a distinct perinuclear ring in the normal cells at 4 h after TNF-alpha exposure. The COX-2 protein levels also increased in cancer cells, but the subcellular distribution was less organized; COX-2 protein appeared diffuse in some cells and accumulated as focal deposits in the cytoplasm of other cells. TNF-alpha induction of COX-2 and prostaglandin E2 correlated inversely with induction of apoptosis. We conclude that COX-2 expression may be important to PrEC cell function. Although it is low in stromal and tumor cells, COX-2 expression is induced by TNF-alpha in these cells, and this responsiveness may play an important role in prostate cancer progression.