IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre-cancerous and cancer lesions
IGF1 mRNA isoform expression in the cervix of HPV-positive women with pre-cancerous and cancer lesions
复制标题
DOI：
10.3892/etm.2010.174
复制
发表时间：
2011-01-01
影响因子：
2.7
通讯作者：
Gozdzicka-Jozefiak, Anna
中科院分区：
文献类型：
--
作者：
Koczorowska, Maria Magdalena;Kwasniewska, Anna;Gozdzicka-Jozefiak, Anna
人乳头瘤病毒（HPV）在宫颈癌病因学中起着至关重要的作用。然而，并非所有感染hpv的妇女都会患上癌症，这表明额外的细胞因素促进了癌变。本研究的目的是分析在hpv依赖性宫颈癌发生过程中，胰岛素样生长因子1 （IGF1）亚型在FOX2、SP1和IGF1受体（IGF1R）表达背景下的表达谱。我们分析了来自宫颈癌前病变和癌前病变妇女的109个上皮组织样本。PCR检测HPV DNA， real-time PCR定量分析分析基因的表达水平。在癌前细胞中，所有IGF1 mRNA剪接异构体都被上调，并且在癌症样本中观察到平衡向有丝分裂IGF1Eb的转变。IGF1的表达主要由PI启动子控制，并且在癌症中观察到P2的使用增加。检测IGF1 mRNA剪接异构体与FOX2剪接因子、P1/P2活性和SP1转录因子表达水平的相关性。IGF1的表达与其受体IGF1R之间无相关性。我们的研究结果表明，IGF1，特别是其剪接谱，可能是宫颈癌发生的另一个预后因素。
Human papillomavirus (HPV) plays a crucial role in cervical cancer etiology. However, not all HPV-infected women develop cancer, indicating that additional cellular factors facilitate carcinogenesis. The aim of this study was to analyze the expression profile of insulin-like growth factor 1 (IGF1) isoforms in the context of FOX2, SP1 and IGF1 receptor (IGF1R) expression during HPV-dependent cervical carcinogenesis. One hundred and nine epithelial tissue samples from women with pre-cancerous and cancer lesions of the cervix were analyzed. HPV DNA was identified by PCR, and real-time PCR was used to quantify the expression levels of the analyzed genes. All IGF1 mRNA splicing isoforms were up-regulated in pre-cancerous cells, and a shift in the balance towards mitogenic IGF1Eb was observed in the cancer samples. IGF1 expression was controlled mainly by the PI promoter, and an increase in P2 usage was observed in the cancer. Correlations between IGF1 mRNA splicing isoforms and the FOX2 splicing factor, as well as P1/P2 activity and SP1 transcription factor expression levels were detected. No correlation was observed between the expression of IGF1 and its receptor IGF1R. Our results suggest that IGF1, in particular its splicing profile, may be an additional prognostic factor in cervical carcinogenesis.