Riggins G J, Thiagalingam S, Rozenblum E, Weinstein C L, Kern S E, Hamilton S R, Willson J K, Markowitz S D, Kinzler K W, Vogelstein B
Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
Nat Genet. 1996 Jul;13(3):347-9. 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.
对转化生长因子β（TGF-β）生长抑制作用的抗性在人类癌症中很常见。然而，肿瘤细胞对TGF-β产生抗性的机制通常尚不清楚。我们已经鉴定出五个与果蝇基因Mad相关的新人类基因，Mad被认为可转导来自TGF-β家族成员的信号。在18例结直肠癌中的2例中发现其中一个基因发生了体细胞突变，另外三个基因位于先前怀疑含有肿瘤抑制基因的染色体位置。这些数据表明，这个基因家族可能在肿瘤形成的抑制中发挥重要作用，赋予TGF-β样配体生长抑制作用。
