Human chromosome 11 suppresses the tumorigenicity of adenovirus transformed baby rat kidney cells: involvement of the Wilms' tumor 1 gene.
Human chromosome 11 was introduced into adenovirus-transformed baby rat kidney (BRK) cells by microcell-mediated chromosome transfer. The resulting microcell hybrids (MCHs) showed a reduced ability to form tumors upon s.c. injection into athymic mice. Further analysis, with the use of defined deletion chromosomes of 11p, indicated that the presence of region 11p13-p12 is necessary for the suppression of tumorigenicity. In contrast, the presence of region 11p15-14.1 appeared to increase the rate of tumor growth. Expression studies on the human Wilms' tumor I (WTI) and the insulin-like growth factor II (IGF-II) genes, which lie in regions 11p13 and 11p15, respectively, suggested the involvement of both genes in determining the degree of suppression of tumorigenicity. Finally, stable expression of a murine WTI protein in the adenovirus-transformed cells resulted in almost complete suppression of tumorigenicity, establishing the WTI protein as a tumor suppressor in this cell system.
Menke
A L
AL
Laboratory for Molecular Carcinogenesis, Leiden University, The Netherlands.
van Ham
R C
RC
Sonneveld
E
E
Shvarts
A
A
Stanbridge
E J
EJ
Miyagawa
K
K
van der Eb
A J
AJ
Jochemsen
A G
AG
D000260:Adenoviruses, Human / Q000235:genetics; D000818:Animals; D002455:Cell Division; D002472:Cell Transformation, Viral; D002880:Chromosomes, Human, Pair 11; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D016162:Genes, Wilms Tumor; D011905:Genes, ras; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000235:genetics*; D051381:Rats; D009396:Wilms Tumor / Q000235:genetics*
D004273:DNA, Neoplasm; D007335:Insulin-Like Growth Factor II