title: TGF-beta signalling pathway factors in HPV-induced cervical lesions.
abstract: 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.
authors: Viral Genetic Engineering Laboratory, Romanian Academy Stefan S. Nicolau Virology Institute, Bucharest, Romania. iulia_iancu2005@yahoo.com
authors: Iulia Virginia
authors: IV
authors: Iancu
authors: Anca
authors: A
authors: Botezatu
authors: Cristina D
authors: CD
authors: Goia-Ruşanu
authors: Anca
authors: A
authors: Stănescu
authors: Irina
authors: I
authors: Huică
authors: Elena
authors: E
authors: Nistor
authors: Gabriela
authors: G
authors: Anton
authors: Adriana
authors: A
authors: Pleşa
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000302:isolation & purification*; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000821:virology; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000378:metabolism* / Q000821:virology
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1