2,3,7,8-Tetrachlorodibenzo-p-dioxin increases mRNA levels for interleukin-1beta, urokinase plasminogen activator, and tumor necrosis factor-alpha in human uterine endometrial adenocarcinoma RL95-2 cells.
This study investigated the potential role of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in uterine growth utilizing a human endometrial adenocarcinoma cell line (RL95-2). Western immunoblot analysis showed a maximal induction of cytochrome P4501A1 (CYP1A1) at 1 nM TCDD, but no change in epidermal growth factor receptor (EGFR) protein level. Northern blot analysis showed that TCDD significantly increased the steady state mRNA level of CYP1A1 and CYP1B1 which was maximal at 1 nM. TCDD significantly increased mRNA levels for interleukin-1beta (IL-1beta) by 6h, and for urokinase plasminogen activator (uPA) and tumor necrosis factor-alpha (TNF-alpha) by 36h. Nuclear runoff analysis showed that transcription of CYP1A1 was significantly increased by TCDD with no effect on CYP1B1, uPA or IL-1beta. These results indicate that TCDD can differentially alter the expression of growth factor and cytokine gene products in uterine cells which may contribute to the promotion of uterine disease.
Charles
G D
GD
Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32610-0267, USA.
Shiverick
K T
KT
D000230:Adenocarcinoma / Q000378:metabolism*; D015153:Blotting, Western; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis*
D007375:Interleukin-1; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014568:Urokinase-Type Plasminogen Activator