p53Arg72Pro多态性与HPV相关宫颈癌发生机制

Correlation Between p53Arg72Pro Polymorphisms and Carcinogenic Mechanism in HPV-associated Cervical Carcinoma

[目的]探讨p53Arg72Pro多态性与HPV相关宫颈癌发生机制的关系。[方法]采用PCR技术检测210例宫颈癌和95例正常宫颈组织的HPV16DNA,采用免疫组化方法及TUNEL检测p53Arg72Pro三种基因型中p53、p21、Bax、Ki-67蛋白(PI)表达以及细胞凋亡(AI)。[结果]宫颈癌HPV16阳性率为70.5%,与正常宫颈组织(7.4%)相比差异具有统计学意义(P<0.05)。HPV16阳性的宫颈癌中:①p53蛋白阴性和弱阳性表达率(73.6%)高于强阳性率(26.4%),其中p53Arg的阴性表达率(39.2%)高于p53Pro(16.7%),差异有统计学意义(P<0.05);②p21蛋白阴性和弱阳性组中,p53Pro型中PI高于p53Arg型,差异有统计学意义(P<0.05);③Bax蛋白阴性和弱阳性组中,p53Pro型中AI低于p53Arg型,差异有统计学意义(P<0.05)。[结论]p53蛋白可被HPV16E6蛋白降解,其中p53Arg蛋白更易被降解;p53Arg和p53Pro蛋白被降解后,两者抑制细胞增殖能力的降低和诱导细胞凋亡能力的降低程度不同,其中p53Pro蛋白转录激活p21和Bax基因的功能及细胞周期阻滞作用的降低更明显。

[Purpose ] To explore the relationship between p53Arg72Pro polymorphisms and carcinogenic mechanism in HPV-associated cervical carcinoma. [Methods] HPV16 DNA was determined by PCR and expressions of p53, p21, Bax, Ki-67 protein （PI） and cellular apoptosis （AI） were detected by immunohistochemistry and TUNEL in different genotypes of p53Arg72Pro of 210 cases with cervical carcinoma and 95 cases with normal cervical tissue. [Results] The positive rate of HPV16 （70.5%） in cervical carcinoma was significantly higher than that in normal cervical tissue （7.4%） （P〈0.05）. Among patients with HPV positive cervical carcinoma,①the expression rate of p53 weak positive and negative（73.6%） was significantly more than those of p53 strong positive （26.4%） and the negative rate of p53Arg （39.2%） was significantly higher than that of p53Pro（16.7%） （P〈0.05）; ②in the weak positive and negative group of p21 protein expression, the PI of p53Pro was significantly higher than that of 53Arg （P〈0.05）; ③in the weak positive and negative group of Bax protein expression , the AI of p53Pro was significantly lower than that of p53Arg （P〈0.05）. [Conclusions] p53 protein may be degraded completely or partly by HPVE6 protein, by which p53Arg protein may be easier to be degraded. When p53Arg and p53Pro are degraded, there are significantly differences in the degree of inhibiting cellular proliferation and inducing cellular apoptosis, and the function of p53Pro protein would be decreased significantly in transcripting p21, Bax gene and blocking cell cycle.