INCREASED MANGANESE SUPEROXIDE-DISMUTASE EXPRESSION SUPPRESSES THE MALIGNANT PHENOTYPE OF HUMAN-MELANOMA CELLS

被引:441
作者
CHURCH, SL
GRANT, JW
RIDNOUR, LA
OBERLEY, LW
SWANSON, PE
MELTZER, PS
TRENT, JM
机构
[1] UNIV MICHIGAN,SCH MED,DEPT PEDIAT,MSRBII C560 1150 W MED CTR DR,ANN ARBOR,MI 48109
[2] UNIV MICHIGAN,SCH MED,DEPT RADIAT ONCOL,ANN ARBOR,MI 48109
[3] UNIV MICHIGAN,SCH MED,DEPT HUMAN GENET,ANN ARBOR,MI 48109
[4] WASHINGTON UNIV,SCH MED,EDWARD MALLINKRODT DEPT PEDIAT,ST LOUIS,MO 63110
[5] WASHINGTON UNIV,SCH MED,DEPT PATHOL,ST LOUIS,MO 63110
[6] UNIV IOWA,RADIAT RES LAB,IOWA CITY,IA 52242
关键词
D O I
10.1073/pnas.90.7.3113
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Introduction of a normal human chromosome 6 into human melanoma cell lines results in suppression of tumorigenicity. This suggests that a gene(s) on chromosome 6 controls the malignant phenotype of human melanoma. Because antioxidants can suppress the tumor-promotion phase of carcinogenesis, and because the antioxidant enzyme manganese superoxide dismutase (MnSOD) has been localized to a region of chromosome 6 frequently lost in melanomas, we have examined the effect of transfecting sense and antisense human MnSOD cDNAs into melanoma cell lines. Cell lines expressing abundant (+)-sense MnSOD-5 cDNAs significantly altered their phenotype in culture and lost their ability to form colonies in soft agar and tumors in nude mice. In contrast, the introduction of antisense MnSOD or +psv2neo had no effect on melanoma tumorigenicity. These findings indicate that stable transfection of MnSOD cDNA into melanoma cell lines exerts a biological effect that mimics that observed after introduction of an entire human chromosome 6.
引用
收藏
页码:3113 / 3117
页数:5
相关论文
共 44 条
[1]   SUPEROXIDE-DISMUTASE INDUCES DIFFERENTIATION IN MICROPLASMODIA OF THE SLIME-MOLD PHYSARUM-POLYCEPHALUM [J].
ALLEN, RG ;
BALIN, AK ;
REIMER, RJ ;
SOHAL, RS ;
NATIONS, C .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1988, 261 (01) :205-211
[2]  
ALLEN RG, 1991, P SOC EXP BIOL MED, V196, P117
[3]  
BARBACID M, 1987, ANN REV BIOCH, V56, P770
[4]   SUPEROXIDE-DISMUTASE INDUCES DIFFERENTIATION OF FRIEND-ERYTHROLEUKEMIA CELLS [J].
BECKMAN, BS ;
BALIN, AK ;
ALLEN, RG .
JOURNAL OF CELLULAR PHYSIOLOGY, 1989, 139 (02) :370-376
[5]   MOLECULAR THEMES IN ONCOGENESIS [J].
BISHOP, JM .
CELL, 1991, 64 (02) :235-248
[6]   MODIFIERS OF FREE-RADICALS INHIBIT INVITRO THE ONCOGENIC ACTIONS OF X-RAYS, BLEOMYCIN, AND THE TUMOR PROMOTER 12-O-TETRADECANOYLPHORBOL 13-ACETATE [J].
BOREK, C ;
TROLL, W .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (05) :1304-1307
[7]   SOD2 - A NEW TYPE OF TUMOR-SUPPRESSOR GENE [J].
BRAVARD, A ;
SABATIER, L ;
HOFFSCHIR, F ;
RICOUL, M ;
LUCCIONI, C ;
DUTRILLAUX, B .
INTERNATIONAL JOURNAL OF CANCER, 1992, 51 (03) :476-480
[8]   PROOXIDANT STATES AND TUMOR PROMOTION [J].
CERUTTI, PA .
SCIENCE, 1985, 227 (4685) :375-381
[9]   HYDROPEROXIDE METABOLISM IN MAMMALIAN ORGANS [J].
CHANCE, B ;
SIES, H ;
BOVERIS, A .
PHYSIOLOGICAL REVIEWS, 1979, 59 (03) :527-605
[10]  
CHEN LB, 1988, ANNU REV CELL BIOL, V4, P155, DOI 10.1146/annurev.cellbio.4.1.155