Alteration of the DCC tumor-suppressor gene in tumorigenic HPV-18 immortalized human keratinocytes transformed by nitrosomethylurea.
Alteration of the DCC tumor-suppressor gene in tumorigenic HPV-18 immortalized human keratinocytes transformed by nitrosomethylurea.
复制标题
亚硝基甲基脲转化的致瘤性 HPV-18 永生化人角质形成细胞中 DCC 肿瘤抑制基因的改变。
作者：
A. Klingelhutz;P. Smith;L. Garrett;J. McDougall
人乳头瘤病毒18型（HPV-18）永生化人角质细胞系（1811）经致癌物亚硝基甲基脲（NMU）处理后在裸鼠体内转化为致瘤性。与亲本1811细胞相比，NMU转化子（1811-NMU- t）显示出额外的染色体改变，包括在分析的两个1811-NMU- t系中有两个18q缺失。限制性片段长度多态性（RFLP）分析表明，两个1811-NMU-T系都丢失了结肠癌（DCC）肿瘤抑制基因18q缺失的一个等位基因。逆转录聚合酶链反应（RT-PCR）显示，与1811或正常角质形成细胞相比，1811- nmu - t细胞中DCC表达缺失或几乎检测不到，这表明1811- nmu - t细胞中剩余的DCC等位基因也发生了改变。这些研究表明，DCC表达的减少或缺失可能是hpv永生化细胞NMU转化为致瘤性的重要步骤。
A human papillomavirus type 18 (HPV-18)-immortalized human keratinocyte cell line (1811) has been transformed to tumorigenicity in nude mice by treatment with the carcinogen nitrosomethylurea (NMU). The NMU transformants (1811-NMU-T) showed additional chromosome alterations as compared with parental 1811 cells, including 18q deletion in two of two 1811-NMU-T lines analysed. Restriction fragment length polymorphism (RFLP) analysis indicated that both 1811-NMU-T lines had lost one allele of the 18q deleted in colon cancer (DCC) tumor-suppressor gene. Reverse transcriptase polymerase chain reaction (RT-PCR) showed that DCC expression was absent or barely detectable in the 1811-NMU-T cells as compared with 1811 or normal keratinocytes, suggesting that the remaining DCC allele in the 1811-NMU-T cells was also altered. These studies indicate that reduction or loss of DCC expression may be an important step in NMU transformation of HPV-immortalized cells to tumorigenicity.