ONCOGENIC POTENTIAL OF GUANINE-NUCLEOTIDE STIMULATORY FACTOR-ALPHA SUBUNIT IN THYROID-GLANDS OF TRANSGENIC MICE

被引:103
作者
MICHIELS, FM
CAILLOU, B
TALBOT, M
DESSARPSFREICHEY, F
MAUNOURY, MT
SCHLUMBERGER, M
MERCKEN, L
MONIER, R
FEUNTEUN, J
机构
[1] INST GUSTAVE ROUSSY,SERV HISTOPATOL A,F-94805 VILLEJUIF,FRANCE
[2] RHONE POULENC RORER SA,F-94400 VITRY,FRANCE
关键词
ALPHA CAMP; ADENOMA; HYPERTHYROIDISM;
D O I
10.1073/pnas.91.22.10488
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
Transgenic mice have been used to address the issue of the oncogenic potential of mutant guanine nucleotide stimulatory factor (G(s)) alpha subunit in the thyroid gland. The expression of the mutant Arg-201 --> His G(s) alpha subunit transgene has been directed to murine thyroid epithelial cells by bovine thyroglobulin promoter, The transgenic animals develop hyperfunctioning thyroid adenomas with increased intracellular cAMP levels and high uptake of [I-125]iodine and produced elevated levels of circulating triiodothyronine and thyroxine. These animals demonstrate that the mutant form of G(s) alpha subunit carries an oncogenic activity, thus supporting the model that deregulation of cAMP level alters growth control in thyroid epithelium. These animals represent models for humans with autonomously functioning thyroid nodules.
引用
收藏
页码:10488 / 10492
页数:5
相关论文
共 27 条
[1]   TRANSGENIC MODELS OF TUMOR-DEVELOPMENT [J].
ADAMS, JM ;
CORY, S .
SCIENCE, 1991, 254 (5035) :1161-1167
[2]  
BLANCIFIORI C, 1979, PATHOLOGY TUMORS ANI, P451
[3]  
BOURNE HR, 1991, NATURE, V349, P117, DOI 10.1038/349117a0
[4]   SUPPRESSION OF RAS-INDUCED TRANSFORMATION OF NIH 3T3 CELLS BY ACTIVATED G-ALPHA(S) [J].
CHEN, JH ;
IYENGAR, R .
SCIENCE, 1994, 263 (5151) :1278-1281
[5]   STRUCTURAL ELEMENTS OF G-ALPHA-SUBUNITS THAT INTERACT WITH G-BETA-GAMMA, RECEPTORS, AND EFFECTORS [J].
CONKLIN, BR ;
BOURNE, HR .
CELL, 1993, 73 (04) :631-641
[6]  
DIRENZO MF, 1992, ONCOGENE, V7, P2549
[7]   THE CYCLIC AMP-MEDIATED STIMULATION OF CELL-PROLIFERATION [J].
DUMONT, JE ;
JAUNIAUX, JC ;
ROGER, PP .
TRENDS IN BIOCHEMICAL SCIENCES, 1989, 14 (02) :67-71
[8]   PHYSIOLOGICAL AND PATHOLOGICAL REGULATION OF THYROID-CELL PROLIFERATION AND DIFFERENTIATION BY THYROTROPIN AND OTHER FACTORS [J].
DUMONT, JE ;
LAMY, F ;
ROGER, P ;
MAENHAUT, C .
PHYSIOLOGICAL REVIEWS, 1992, 72 (03) :667-697
[9]   GERMLINE MUTATIONS IN THE THYROTROPIN RECEPTOR GENE CAUSE NON-AUTOIMMUNE AUTOSOMAL-DOMINANT HYPERTHYROIDISM [J].
DUPREZ, L ;
PARMA, J ;
VANSANDE, J ;
ALLGEIER, A ;
LECLERE, J ;
SCHVARTZ, C ;
DELISLE, MJ ;
DECOULX, M ;
ORGIAZZI, J ;
DUMONT, J ;
VASSART, G .
NATURE GENETICS, 1994, 7 (03) :396-401