Mad -related genes in the human

• Published in: Nature genetics Vol. 13; no. 3; pp. 347 - 349
• Main Authors: Riggins, Gregory J, Thiagalingam, Sam, Rozenblum, Ester, Weinstein, Craig L, Kern, Scott E, Hamilton, Stanley R, Willson, James K.V, Markowitz, Sanford D, Kinzler, Kenneth W, Vogelstein, Bert
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 01-07-1996
• Subjects: Amino Acid Sequence; Base Sequence; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biological and medical sciences; Chromosome Mapping; Chromosomes, Human, Pair 18; Classical genetics, quantitative genetics, hybrids; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; DNA Mutational Analysis; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drosophila; Fundamental and applied biological sciences. Psychology; Genes, Tumor Suppressor; Genetics of eukaryotes. Biological and molecular evolution; Human; Humans; Molecular Sequence Data; Repressor Proteins; Sequence Alignment; Sequence Homology, Amino Acid; Signal Transduction; Smad1 Protein; Smad2 Protein; Smad4 Protein; Trans-Activators; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Tumor Cells, Cultured; Human; Nucleotide sequence; Transforming growth factor β; Homology; Somatic mutation; Resistance; Signal transduction; Complementary DNA; Gene; Rectum; Digestive diseases; Intestinal disease; Genetics; Multigene family; Tumor; Colon; Expressed sequence tag
• ISSN: 1061-4036; 1546-1718
• DOI: 10.1038/ng0796-347

Resistance to the growth inhibitory effects of TGF-beta is common in human cancers. However, the mechanism(s) by which tumour cells become resistant to TGF-beta are generally unknown. We have identified five novel human genes related to a Drosophila gene called Mad which is thought to transduce signals from TGF-beta family members. One of these genes was found to be somatically mutated in two of eighteen colorectal cancers, and three of the other genes were located at chromosomal positions previously suspected to harbor tumour suppressor genes. These data suggest that this gene family may prove to be important in the suppression of neoplasia, imparting the growth inhibitory effects of TGF-beta-like ligands.