Decreased programmed cell death in the uterine cervix associated with high risk human papillomavirus infection.
Decreased programmed cell death in the uterine cervix associated with high risk human papillomavirus infection.
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DOI：
10.1053/paor.1999.0161
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发表时间：
1999-01-01
期刊：
影响因子：
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通讯作者：
Pillai, M R
中科院分区：
文献类型：
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作者：
Nair, P;Nair, K M;Pillai, M R
研究了宫颈肿瘤进展的各个阶段中细胞凋亡、细胞凋亡调节蛋白、细胞增殖与人乳头瘤病毒感染之间的关系。细胞凋亡通过形态学标准和TUNEL 测定来定义。通过免疫细胞化学评估 p53、bcl-2、bax、cyclin D1、Ki 67 和 E6 蛋白的表达。使用突变体特异性 ELISA 检测突变体 p53 的存在。使用类型特异性引物通过 PCR 确定 HPV 感染类型。细胞凋亡与组织学异常的增加呈显着负相关（p=0.0005）。较高的肿瘤细胞增殖与组织学异常的增加相关（Ki 67 和细胞周期蛋白 D1 的 p=0.001）。 p53 (p=0.0001)和bcl-2 (p=0.0002)的组织学分级和免疫反应性之间存在显着相关性。然而，230 个样本中只有 12 个表达了突变型 p53。 bax 的表达和 bax/bcl-2 比率显示与组织学分级呈负相关（分别为 p=0.0003 和 0.0001）。细胞凋亡程度与 p53 (p=0.0001) 和 bcl-2 (p=0.0001) 的免疫反应性之间也存在负相关。 bax 蛋白的表达与细胞凋亡之间存在显着的正相关性（p=0.0001）。 HPV 感染与组织学异常程度显着相关（p=0.0001）。高危 HPV-E6 蛋白也显示出这种显着相关性 (p=0.0002)。细胞凋亡与HPV感染之间呈负相关(p=0.0002)。高危 HPV 感染与细胞凋亡减少以及人类细胞增殖增加有关。 bax/bcl-2 比率的最低水平也与 HPV 16 和 18 感染相关 (p=0.0001)。高危HPV感染对细胞凋亡和细胞凋亡调节蛋白的调节可能是宫颈癌发生发展的重要因素。
The relationship between apoptosis, apoptosis regulatory proteins, cell proliferation and human papillomavirus infection during various phases of tumor progression in the uterine cervix was studied. Apoptosis was defined by morphological criteria and the TUNEL assay. Expression of p53, bcl-2, bax, cyclin D1, Ki 67 and E6 protein was evaluated by immunocytochemistry. Presence of mutant p53 was detected using a mutant specific ELISA. Type of HPV infection was determined by PCR using type specific primers. Apoptosis showed significant negative correlation with increasing histological abnormality (p=0.0005). Higher tumor cell proliferation was associated with increasing histological abnormality (p=0.001 for Ki 67 and cyclin D1). There was significant correlation between histological grade and immunoreactivity of p53 (p=0.0001 ) and bcl-2 (p=0.0002). However, mutant p53 was expressed by only 12 of the 230 samples. Expression of bax and the bax/bcl-2 ratio showed an inverse correlation to histological grade (p=0.0003 and 0.0001, respectively). There was also an inverse correlation between extent of apoptosis and immunoreactivity of p53 (p=0.0001) and bcl-2 (p=0. 0001). A significant positive correlation between expression of the bax protein and apoptosis was evident (p=0.0001). HPV infection significantly correlated to the extent of histological abnormality (p=0.0001). High risk HPV-E6 protein also showed this significant correlation (p=0.0002). There was an inverse correlation between apoptosis and HPV infection (p=0.0002). High risk HPV infection was associated with decreased apoptosis and also increased human cell proliferation. Lowest levels of bax/bcl-2 ratio was also associated with HPV 16 and 18 infection (p=0.0001). Modulation of apoptosis and apoptotic regulatory proteins by high risk HPV infection may be an important factor in the development of cervical cancer.