人宫颈癌FHIT基因的表达改变与HPV16感染的关系

　　【摘要】 目的 探讨FHIT基因表达改变和HPV16感染与人宫颈癌发生的关系。方法 采用反转录-巢式聚合酶链反应方法测定5种人宫颈癌细胞株(SiHa、HeLa、RJC-1、CS1213、C4-1)和58例宫颈癌组织与18例正常宫颈对照中FHIT mRNA的表达;回收7例FHIT基因不同的转录扩增产物，纯化后进行DNA测序;PCR技术检测组织中HPV16型的感染状况。结果 SiHa、HeLa和C4-1宫颈癌细胞中有FHIT基因转录异常; 宫颈癌组织中39例(67.2%)存在FHIT基因异常表达，显著高于正常对照组0例(0%)(P<0.05);37例(63.8%)有HPV16感染，显著高于正常对照组1例(5.0%)(P<0.05)。宫颈癌组织中有HPV16感染患者的FHIT基因表达异常数(30/37)显著高于HPV16未感染的患者(9/21)，二者之间存在相关性(P<0.01);FHIT基因的异常表达和HPV16的感染与患者的年龄、临床分期、肿瘤直径、病理分级及是否伴淋巴结转移无相关性(P>0.05)。序列分析发现FHIT基因转录本主要存在不同程度的外显子的缺失，以第5位和第6位外显子的缺失为主，未见未知序列的插入和点突变。结论 FHIT基因在人宫颈癌组织中的异常表达率明显增高，且与HPV16的感染有关，这些改变可能在人宫颈鳞癌的发生中起着重要作用。

　　【关键词】 宫颈癌;FHIT基因;基因缺失;人乳头瘤病毒(HPV)

　　Fragile histidine triad transcription abnormalities and human　papillomavirus16 infection in human cervical carcinoma

　　Han Jin, Chen Wei, Li Xu

　　Center for Laboratory Medicine, the First Affiliated Hospital,Medical School of Xi’an Jiaotong University, Xi’an 710061, China

　　ABSTRACT: Objective To evaluate the relationship between fragile histidine triad (FHIT) transcription abnormalities and HPV16 infection and human cervical tumorigenesis. Methods Total RNA from 5 cervical carcinoma cell lines (SiHa, HeLa, RJC-1, CS1213 and C4-1), 58 primary cervical cancer specimens and 18 normal cervical epithelial tissues were extracted and FHIT transcripts were characterized by a two-step(nested) reverse transcription (RT)-PCR. The seven of the PCR products with different size were purified and sequenced. HPV16 infection was assessed by PCR. Results ① There were altered FHIT transcripts in SiHa, HeLa and C4-1 cells. Aberrant FHIT transcripts were detected in 39 out of the 58 cervical cancer samples (67.2%), but none out of 18 in the normal cervix tissue specimens (0%); HPV16 infections were identified in 37 of the 58 cervical cancer tissues (63.8%), but 1 in the 18 normal cervical epithelial tissues (5%), which showed a significant difference between these two groups (P<0.05). ② The number of part

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