Studies on Pathogenesis of Cervical Carcinoma Based on the Analysis of Growth and Differentiation Mechanism of Cervical Squamous Epithelium

宫颈鳞状上皮中朗格汉斯细胞和宫颈粘液中的免疫球蛋白和免疫球蛋白A的分析表明，宫颈在月经周期的卵泡期具有局部防御机制。对正常宫颈细胞增殖抗原Ki-67的分析表明，副基细胞在黄体期比在卵泡期更频繁地进入细胞周期。基本细胞和储备细胞通常处于休眠状态，但少数细胞在黄体期和妊娠期进入细胞周期。由于周期细胞对病毒感染更敏感，黄体期和妊娠期的基础和/或储备细胞可能面临感染HPV的风险。雌激素受体(ER)、孕激素受体(PR)、表皮生长因子受体(EGFR)和C-erbB-2蛋白的表达是调节正常宫颈鳞状上皮生长和分化的因素。然而，…HPV感染的宫颈鳞状上皮表现为ER表达下调，PR表达上调，这是正常宫颈鳞状细胞增殖的受体状态特征。此外，将HPV16DNA导入ER阳性的乳腺癌细胞(ZR-75-1)，可使其ER表达下调。提示HPV DNA直接影响ER的表达。此外，PR在HPV感染的鳞状肿瘤中的表达上调表明，孕酮通过HPV的糖皮质激素反应元件促进了HPV感染的鳞状上皮的增殖。此外，在HPV感染的鳞状上皮中，EGFR表达上调，C-erbB-2蛋白表达下调。C-erbB-2蛋白的表达与正常宫颈上皮的分化密切相关，提示HPV感染影响宫颈鳞状细胞的分化。ADF/硫氧还蛋白和HPVDan在宫颈鳞癌组织中的共同表达提示ADF-表达与HPV DNA复制密切相关。总而言之，与月经周期无关的人类性行为可能是HPV感染的内在风险。HPV感染可能导致鳞状细胞增殖的受体状态ER和PR表达下调，EGFR表达上调和C-erbB-2蛋白表达下调，ADF-α表达异常。提示HPV感染与宫颈鳞状细胞癌变密切相关。较少

The analysis of Langerhans cell in the cervical squamous epithelium, and IgG and IgA in the cervical mucus revealed that the cervix possesses a local defense mechanism in the follicular phase of the menstrual cycle. Analysis of a cell proliferation antigen Ki-67 in normal cervix revealed that parabasel cells enter the cell cycle more frequently in the luteal phase than in the follicular phase. Basal and reserve cells are usually resting, but a few cells enter the cell cycle during the luteal phase and during pregnancy. Since cycling cells are more susceptible to viral infection, the basal and/or reserve cells during the luteal phase and pregnancy are suggested to be under the risk of human papillomavirus (HPV) infection. As factors regulationg growth and differentiation of normal cervical squamous epithelium, sex steroids through the expression of estrogen receptors(ER) and progesterone receptors (PR), epidermal growth factor receptor (EGFR), and C-erbB-2 protein were suggested. Howeve … More r, the squamous epithelium infected by HPV showed down-expression of ER and up-expression of PR which were the characteristics of receptor status of normal cervical squamous proliferation. Moreover, transfection of HPV 16 DNA into the ER-positive mammary cancer cell line (ZR-75-1) resulted in its down-expression of ER. This suggested that HPV DNA directly affects the expression of ER. Moreover, up-expression of PR in the HPV-infected squamous neoplasia suggested that, through the glucocorticoid responsive element of HPV, progesterone promotes the proliferation of HPV-infected squamous epithelium. In addition, up-expression of EGFR and down-expression of C-erbB-2protein were observed in the HPV-infected squamous epithelium. Since C-erbB-2 protein expression was closely associated with the differentiation of normal cervical epithelium, these results suggest that HPV-infection affects the differentiation of cervical squamous cells. And co- expression of ADF/thioredoxin and HPV DAN in the neoplastic cervical squamous epithelium suggest that ADF-expression is closely associated with HPV DNA replication. In summary, a human sexual behavior irrespective of the menstrual cycle may be an inherent risk for HPV-infection. HPV infection possibly induces down-expression of ER and up- expression of PR which are the receptor status of squamous proliferation, and up-expression of EGFR and down expression of C-erbB-2 protein, and abnormal ADF-expression. These results suggest that HPV infection is deeply involved in the neoplastic transformation of cervical squamous cells. Less