Tsujiuchi T, Sasaki Y, Tsutsumi M, Konishi Y
Department of Oncological Pathology, Cancer Center, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
Jpn J Cancer Res. 2000 Nov;91(11):1090-5. doi: 10.1111/j.1349-7006.2000.tb00889.x.
Mutations and expression of the transforming growth factor-beta receptor type II (TGF-beta RII) gene were investigated in lung adenocarcinomas induced by N-nitrosobis(2-hydroxypropyl)amine (BHP) in rats. Males of the Wistar strain, 6 weeks old, were given 2000 ppm of BHP in their drinking water for 12 weeks and then maintained without further treatment until killed at week 25. Total RNA was extracted from 12 adenocarcinomas and mutations in TGF-beta RII were investigated by RT-PCR-restriction-SSCP analysis followed by sequencing analysis. Two out of 12 adenocarcinomas showed band shifts, indicative of mutations (16.7%). One was a CTG-to-TTG (Leu to Leu) transition at codon 308 without amino acid alteration and the other a frameshift deletion of one of two guanines at nucleotides 1434 to 1435 (codon 477 to 478). Semi-quantitative RT-PCR analysis demonstrated significantly reduced TGF-beta RII expression in adenocarcinomas, as compared with normal lung tissue. These results suggest that TGF-beta RII alterations may play a role in the acquisition of growth advantage by lung adenocarcinomas induced by BHP in rats.
研究了N-亚硝基双（2-羟丙基）胺（BHP）诱导的大鼠肺腺癌中转化生长因子βⅡ型受体（TGF-βRII）基因的突变和表达情况。6周龄的雄性Wistar大鼠，饮用含2000 ppm BHP的水12周，然后不再进行进一步处理，直至在第25周处死。从12个腺癌中提取总RNA，通过RT-PCR-限制性单链构象多态性分析（RT-PCR-restriction-SSCP analysis）及后续测序分析研究TGF-βRII的突变情况。12个腺癌中有2个出现条带迁移，表明存在突变（16.7%）。一个是密码子308处的CTG到TTG（亮氨酸到亮氨酸）的转换，氨基酸未发生改变；另一个是核苷酸1434至1435处（密码子477至478）两个鸟嘌呤中的一个发生移码缺失。半定量RT-PCR分析表明，与正常肺组织相比，腺癌中TGF-βRII的表达显著降低。这些结果表明，TGF-βRII改变可能在BHP诱导的大鼠肺腺癌获得生长优势中发挥作用。
