MADR2 maps to 18q21 and encodes a TGF beta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma

被引：770

作者：

Eppert, K

Scherer, SW

Ozcelik, H

Pirone, R

Hoodless, P

Kim, H

Tsui, LC

Bapat, B

Gallinger, S

Andrulis, IL

Thomsen, GH

Wrana, JL

Attisano, L

机构：

[1] HOSP SICK CHILDREN,DEPT GENET,TORONTO,ON M5G 1X8,CANADA

[2] MT SINAI HOSP,DEPT LAB MED & PATHOL,TORONTO,ON M5G 1X8,CANADA

[3] MT SINAI HOSP,DEPT SURG,TORONTO,ON M5G 1X8,CANADA

[4] MT SINAI HOSP,SAMUEL LUNENFELD RES INST,TORONTO,ON M5G 1X8,CANADA

[5] UNIV TORONTO,DEPT MOL & MED GENET,TORONTO,ON M5S 1A8,CANADA

[6] UNIV TORONTO,DEPT ANAT & CELL BIOL,TORONTO,ON M5S 1A8,CANADA

[7] UNIV TORONTO,DEPT CELLULAR & MOL PATHOL,TORONTO,ON M5S 1A8,CANADA

[8] SUNY STONY BROOK,DEPT BIOCHEM & CELL BIOL,INST CELL & DEV BIOL,STONY BROOK,NY 11794

来源：

CELL | 1996年 / 86卷 / 04期

基金：

英国医学研究理事会; 美国国家科学基金会;

关键词：

D O I：

10.1016/S0092-8674(00)80128-2

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：

The MAD-related (MADR) family of proteins are essential components in the signaling pathways of serine/threonine kinase receptors for the transforming growth factor beta (TGF beta) superfamily. We demonstrate that MADR2 is specifically regulated by TGF beta and not bone morphogenetic proteins. The gene for MADR2 was found to reside on chromosome 18q21, near DPC4, another MADR protein implicated in pancreatic cancer. Mutational analysis of MADR2 in sporadic tumors identified four missense mutations in colorectal carcinomas, two of which display a loss of heterozygosity. Biochemical and functional analysis of three of these demonstrates that the mutations are inactivating. These findings suggest that MADR2 is a tumor suppressor and that mutations acquired in colorectal carcinomas may function to disrupt TGF beta signaling.

引用

页码：543 / 552

页数：10

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[41] MESODERMAL PATTERNING BY AN INDUCER GRADIENT DEPENDS ON SECONDARY CELL-CELL COMMUNICATION [J].