A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-κB or ODC transactivation

被引:163
作者
Yang, HS [1 ]
Jansen, AP
Nair, R
Shibahara, K
Verma, AK
Cmarik, JL
Colburn, NH
机构
[1] NCI, Basic Res Lab, Gene Regulat Sect, Frederick, MD 21702 USA
[2] Univ Wisconsin, Sch Med, Dept Human Oncol, Madison, WI 53792 USA
[3] Kyoto Univ, Sakyo Ku, Kyoto 606, Japan
关键词
pdcd4; AP-1; NF-kappa B; transformation;
D O I
10.1038/sj.onc.1204137
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
Pdcd4 is a novel transformation suppressor that is highly expressed in promotion-resistant (P-) mouse epidermal JB6 cells but not in susceptible (P+) cells. Overexpression of pdcd4 cDNA in stably transfected P+ cells rendered cells resistant to tumor promoter-induced transformation, indicating that elevated expression of Pdcd4 protein is sufficient to suppress neoplastic transformation. To determine whether Pdcd4 suppresses neoplastic transformation through inhibiting known transformation required events, se examined the possibility that pdcd4 inhibited the activation of AP-1 or NF-kappaB dependent transcription or of ornithine decarboxylase (ODC) activity. Activation of AP-1-dependent transcriptional activity mas inhibited bai pdcd4 expression in a concentration dependent manner. In contrast, Pdcd4 slightly increased NF-kappaB-dependent transcription and did not alter ODC enzymatic activity. Previous studies suggested that activation of AP-1 was required for P+ cell transformation as well as for tumor promotion in vivo. These results indicate that Pdcd4 functions as a transformation suppressor, possibly through inhibiting AP-1 activation in combination with other factors such as enhancing NF-kappaB activation. Pdcd4 may thus constitute a useful molecular target for cancer prevention.
引用
收藏
页码:669 / 676
页数:8
相关论文
共 44 条
[1]  
AMSTAD P, 1994, J BIOL CHEM, V269, P1606
[2]   Manganese superoxide dismutase expression inhibits soft agar growth in JB6 clone41 mouse epidermal cells [J].
Amstad, PA ;
Liu, H ;
Ichimiya, M ;
Berezesky, IK ;
Trump, BF .
CARCINOGENESIS, 1997, 18 (03) :479-484
[3]   THE ROLE OF JUN, FOS AND THE AP-1 COMPLEX IN CELL-PROLIFERATION AND TRANSFORMATION [J].
ANGEL, P ;
KARIN, M .
BIOCHIMICA ET BIOPHYSICA ACTA, 1991, 1072 (2-3) :129-157
[4]  
Azzoni L, 1998, J IMMUNOL, V161, P3493
[5]   The NF-kappa B and I kappa B proteins: New discoveries and insights [J].
Baldwin, AS .
ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :649-683
[6]   c-Rel arrests the proliferation of HeLa cells and affects critical regulators of the G(1)/S-phase transition [J].
Bash, J ;
Zong, WX ;
Gelinas, C .
MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (11) :6526-6536
[7]   Tumor promotion resistant cells are deficient in AP-1 DNA binding, JunD DNA binding and JunD expression and form different AP-1-DNA complexes than promotion sensitive cells [J].
Bernstein, LR ;
Walker, SE .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 1999, 1489 (2-3) :263-280
[8]   APL/JUN FUNCTION IS DIFFERENTIALLY INDUCED IN PROMOTION-SENSITIVE AND RESISTANT JB6 CELLS [J].
BERNSTEIN, LR ;
COLBURN, NH .
SCIENCE, 1989, 244 (4904) :566-569
[9]   Activation-dependent transcriptional regulation of the human fas promoter requires NF-κB p50-p65 recruitment [J].
Chan, H ;
Bartos, DP ;
Owen-Schaub, LB .
MOLECULAR AND CELLULAR BIOLOGY, 1999, 19 (03) :2098-2108
[10]  
Chang PL, 2000, J CELL BIOCHEM, V78, P8, DOI 10.1002/(SICI)1097-4644(20000701)78:1<8::AID-JCB2>3.3.CO