Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells

被引:235
作者
Shao, JY
Sheng, HM
Inoue, H
Morrow, JD
DuBois, RN
机构
[1] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Vet Affairs Med Ctr,Dept Med, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Vet Affairs Med Ctr,Dept Pharmacol, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Vet Affairs Med Ctr,Dept Cell Biol, Nashville, TN 37232 USA
[4] Natl Cardiovasc Ctr, Res Inst, Dept Pharmacol, Suita, Osaka 5658565, Japan
关键词
D O I
10.1074/jbc.M002324200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cyclooxygenase-2 (COX-2) is not normally expressed in the human large intestine, but its levels are increased in the majority of human colorectal carcinomas, Here we investigate the regulation of constitutive COX-2 expression and prostaglandin production in human colorectal carcinoma cells. Both COX-2 mRNA and protein were expressed in well differentiated HCA-7, Moser, LS-174, and HT-29 cells, albeit at different levels. COX-2 expression was not detected in several poorly differentiated colon cancer cell lines including DLD-1, Transcriptional regulation played a key role for the expression of COX-2 in human colon carcinoma cells, and both the nuclear factor for interleukin-6 regulatory element and the cAMP-response element were responsible for regulation of COX-2 transcription. COX-2 mRNA was more stable in HCA-7 cells than in the other cell lines tested. Both transcriptional and post-transcriptional regulation of COX-2 involved the MAP kinase pathway. Modulation of the Akt/protein kinase B or Rho B signaling pathways altered the levels of COX-2 expression. Furthermore, COX-2 protein is degraded through ubiquitin proteolysis, and its half-life was similar to3.5-8 h, HCA-7 cells produced significant quantities of prostaglandin E-2 and other prostaglandins. Moser and LS-174 cells also generated prostaglandins, but levels were significantly lower than that observed in HCA-7 cells.
引用
收藏
页码:33951 / 33956
页数:6
相关论文
共 57 条
[1]   Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily [J].
Anderson, MJ ;
Viars, CS ;
Czekay, S ;
Cavenee, WK ;
Arden, KC .
GENOMICS, 1998, 47 (02) :187-199
[2]   Cloning and characterization of AFX, the gene that fuses to MLL in acute leukemias with a t(X;11)(q13;q23) [J].
Borkhardt, A ;
Repp, R ;
Haas, OA ;
Leis, T ;
Harbott, J ;
Kreuder, J ;
Hammermann, J ;
Henn, T ;
Lampert, F .
ONCOGENE, 1997, 14 (02) :195-202
[3]   Phosphatidylinositol 3-kinase couples the interleukin-2 receptor to the cell cycle regulator E2F [J].
Brennan, P ;
Babbage, JW ;
Burgering, BMT ;
Groner, B ;
Reif, K ;
Cantrell, DA .
IMMUNITY, 1997, 7 (05) :679-689
[4]   Localization of cyclooxygenase-2 in human sporadic colorectal adenomas [J].
Chapple, KS ;
Cartwright, EJ ;
Hawcroft, G ;
Tisbury, A ;
Bonifer, C ;
Scott, N ;
Windsor, ACJ ;
Guillou, PJ ;
Markham, AF ;
Coletta, PL ;
Hull, MA .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 156 (02) :545-553
[5]   Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery [J].
Datta, SR ;
Dudek, H ;
Tao, X ;
Masters, S ;
Fu, HA ;
Gotoh, Y ;
Greenberg, ME .
CELL, 1997, 91 (02) :231-241
[6]   STRUCTURAL CHARACTERIZATION OF THE FKHR GENE AND ITS REARRANGEMENT IN ALVEOLAR RHABDOMYOSARCOMA [J].
DAVIS, RJ ;
BENNICELLI, JL ;
MACINA, RA ;
NYCUM, LM ;
BIEGEL, JA ;
BARR, FG .
HUMAN MOLECULAR GENETICS, 1995, 4 (12) :2355-2362
[7]  
delPeso L, 1997, SCIENCE, V278, P687
[8]   Post-transcriptional control of cyclooxygenase-2 gene expression -: The role of the 3′-untranslated region [J].
Dixon, DA ;
Kaplan, CD ;
McIntyre, TM ;
Zimmerman, GA ;
Prescott, SM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (16) :11750-11757
[9]   CREB is a regulatory target for the protein kinase Akt/PKB [J].
Du, KY ;
Montminy, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (49) :32377-32379
[10]   REGULATION OF EICOSANOID PRODUCTION AND MITOGENESIS IN RAT INTESTINAL EPITHELIAL-CELLS BY TRANSFORMING GROWTH-FACTOR-ALPHA, AND PHORBOL ESTER [J].
DUBOIS, RN ;
AWAD, J ;
MORROW, J ;
ROBERTS, LJ ;
BISHOP, PR .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (02) :493-498