R719Q突变导致PTCH2基因抑癌功能丧失

摘要

Objective To investigate the effect of mutated PTCH2 that caused the nevoid basal cell carcinoma syndrome (NBCCS) on carcinoma cells.Methods Squamous cell carcinoma cell line SCC1 was infected with retroviral construction of empty vector,wild-type PTCH2 and PTCH2 with R719Q mutant to establishthe stably transfected cell lines.Cell growth curve was used to observe cell proliferation and tumorigenecity of nude mice subcutaneously transplanted by cancer cells.Results The over-expression of wild-type PTCH2 inhibited the SCC1 cell proliferation in vitro,and also inhibited tumor formation in vivo,but PTCH2 with R719Q mutant lost this suppression function.Conclusion PTCH2 with R719Q mutant that caused NBCCS resulted in the loss of tumor suppression function in carcinoma cells.%目的 研究痣样基底细胞癌综合征(NBCCS)致病基因PTCH2突变后对肿瘤细胞的影响.方法 在鳞状细胞癌细胞系SCC1中利用逆转录病毒构建PTCH2的野生型及R719Q突变型的稳定转染细胞系,利用体外细胞增殖实验及体内裸鼠皮下成瘤实验,探讨PTCH2对肿瘤细胞成瘤能力的影响.结果 过表达野生型PTCH2抑制SCC1细胞的体外增殖能力,并且抑制SCC1细胞的体内成瘤能力,而R719Q突变型的PTCH2则丧失了这种抑制能力.结论 痣样基底细胞癌综合征致病性突变PTCH2-R719Q导致PTCH2对肿瘤细胞抑制作用的丧失.