Vincent F, Hagiwara K, Ke Y, Stoner G D, Demetrick D J, Bennett W P
Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Biochem Biophys Res Commun. 1996 Jun 25;223(3):561-4. doi: 10.1006/bbrc.1996.0934.
The transforming growth factor beta (TGF beta) binds the type II TGF beta growth factor receptor (TGF beta RII) to inhibit growth of most epithelial tissues. Most human colon cancers with microsatellite instability have frameshift mutations in two microsatellites within the TGF beta RII coding region; such mutations truncate the receptor to produce resistance to TGF beta. To investigate this pathway in other tissues, we surveyed sporadic human cancers of the pancreas, liver and breast to determine the frequency of microsatellite mutations in the TGF beta RII. We amplified genomic DNA segments containing two microsatellites plus 72% of domain XI of the serine-threonine kinase region. SSCP analysis showed no evidence of mutation in 32 sporadic cancers (12 pancreas, 10 liver, and 10 breast). We conclude that microsatellite mutations in TGF beta RII are uncommon in sporadic tumors of the pancreas, liver and breast.
转化生长因子β(TGFβ)与II型TGFβ生长因子受体(TGFβRII)结合,以抑制大多数上皮组织的生长。大多数具有微卫星不稳定性的人类结肠癌在TGFβRII编码区域内的两个微卫星中存在移码突变;此类突变使受体截短,从而产生对TGFβ的抗性。为了研究其他组织中的这一途径,我们对散发性胰腺癌、肝癌和乳腺癌进行了调查,以确定TGFβRII中微卫星突变的频率。我们扩增了包含两个微卫星以及丝氨酸 - 苏氨酸激酶区域第XI结构域72%的基因组DNA片段。单链构象多态性分析显示,在32例散发性癌症(12例胰腺、10例肝脏和10例乳腺)中没有突变迹象。我们得出结论,TGFβRII中的微卫星突变在散发性胰腺、肝脏和乳腺肿瘤中并不常见。