THE TUMOR-SUPPRESSOR GENE WT1 INHIBITS RAS-MEDIATED TRANSFORMATION

被引:0
作者
LUO, XN
REDDY, JC
YEYATI, PL
IDRIS, AH
HOSONO, S
HABER, DA
LICHT, JD
ATWEH, GF
机构
[1] CUNY MT SINAI SCH MED, DEPT MED, NEW YORK, NY 10029 USA
[2] CUNY MT SINAI SCH MED, BROOKDALE CTR MOLEC BIOL, NEW YORK, NY 10029 USA
[3] MASSACHUSETTS GEN HOSP, CTR CANC, GENET MOLEC LAB, BOSTON, MA 02129 USA
[4] HARVARD UNIV, SCH MED, BOSTON, MA 02129 USA
关键词
WT1; TUMOR SUPPRESSORS; RAS-TRANSFORMATION;
D O I
暂无
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
Wilms' tumor belongs to a small group of pediatric neoplasms that have served as paradigms of human cancers in which recessive mutations play a primary role in tumorigenesis. WT1 is a candidate tumor suppressor gene that is mutationally inactivated in a proportion of both familial and sporadic Wilms' tumors. Recent studies demonstrated that WT1 can partially suppress growth of a Wilms' tumor cell line in vitro and in vivo. We investigated the ability of WT1 to inhibit the expression of the transformed phenotype in non-Wilms' tumor cells. The expression of WT1 cDNA in ras-transformed NIH3T3 cells yielded large, flat cells that exhibited complete contact-inhibition. These morphologic changes were associated with decreased proliferation, suppression of clonogenicity in soft agar and inhibition of tumor growth in nude mice. Moreover, expression of WT1 in non-transformed NIH3T3 cells resulted in similar morphologic changes and profound resistance to transformation by an activated uas oncogene. These studies suggest that tumor inhibition by WT1 in these cells may be achieved by interference with the ras-mediated signalling pathway.
引用
收藏
页码:743 / 750
页数:8
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