Iancu Iulia Virginia, Botezatu Anca, Goia-Ruşanu Cristina D, Stănescu Anca, Huică Irina, Nistor Elena, Anton Gabriela, Pleşa Adriana
Viral Genetic Engineering Laboratory, Romanian Academy Stefan S. Nicolau Virology Institute, Bucharest, Romania.
Roum Arch Microbiol Immunol. 2010 Jul-Sep;69(3):113-8.
Human papillomaviruses (HPV) are considered the etiological agents of cervical cancer, especially high-risk genotypes. TGF-beta (transforming growth factor-beta) is well known for its anti-proliferative effects but the neoplastic cells often lose their sensitivity to TGF-beta. A characteristic alteration associated with malignant progression is the loss of responsiveness to TGF-beta1-induced cell growth inhibition. The aim of the present study was to establish the possible role of some members of TGF-beta signalling pathway during cervical cancer development and the possible relationship with HPV infection. In order to establish TGF-beta gene expression levels in cervical oncogenesis, TGF-beta1, TGF-beta1 receptors and Smad2 were investigated in precancerous and cervical cancer samples (Quantitative Real-Time PCR). The study revealed that 84.5% of patients were positive for HPV DNA. The most prevalent HPV genotypes were high-risk HPV 16 and 18 in single or co-infections. Expression of TGF-beta1 decreased as tumor cells progressed from cervical intraepithelial neoplasia to cervical carcinoma. Furthermore, we observed that cervical lesions without HPV infection expressed significantly less TGF-beta1. TGF-betaRI and Smad2 gene expression levels were found to be decreased in SCC and AC samples in contrast with CIN1 and CIN2/3 samples. Our results showed that in human cervical cancer the disruption of TGF-beta/Smad signalling pathway might contribute to the malignant progression of cervical dysplasia. These data emphasize the importance of canonical TGF-beta pathway integrity in carcinogenesis.
人乳头瘤病毒（HPV）被认为是宫颈癌的病原体，尤其是高危基因型。转化生长因子-β（TGF-β）以其抗增殖作用而闻名，但肿瘤细胞通常会失去对TGF-β的敏感性。与恶性进展相关的一个特征性改变是对TGF-β1诱导的细胞生长抑制反应性丧失。本研究的目的是确定TGF-β信号通路的某些成员在宫颈癌发生过程中的可能作用以及与HPV感染的可能关系。为了确定TGF-β基因在宫颈肿瘤发生中的表达水平，对癌前和宫颈癌样本中的TGF-β1、TGF-β1受体和Smad2进行了研究（定量实时PCR）。研究显示，84.5%的患者HPV DNA呈阳性。最常见的HPV基因型是高危型HPV 16和18，可为单一感染或合并感染。随着肿瘤细胞从宫颈上皮内瘤变发展为宫颈癌，TGF-β1的表达降低。此外，我们观察到未感染HPV的宫颈病变中TGF-β1的表达明显较低。与CIN1和CIN2/3样本相比，SCC和AC样本中TGF-βRI和Smad2基因表达水平降低。我们的结果表明，在人类宫颈癌中，TGF-β/Smad信号通路的破坏可能有助于宫颈发育异常的恶性进展。这些数据强调了经典TGF-β通路完整性在致癌过程中的重要性。
