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WWP1, TGF β and KLF5 gene expression levels as new possible factors involved in cervical oncogenesis
Anca Botezatu, Cristina D. Goia-Ruşanu, Anca D. Stănescu, Iulia V. Iancu, Elena Popa, Elena Nistor, Irina Huica, Gabriela Anton, Adriana Pleşa
Abstract: Infection with human papilloma virus (HPV) is the main cause of cervical cancer. Host genetic alterations, like modifications of gene expression levels can be induced as a response to the viral infection. Kruppel-like factor 5 (KLF5) is a transcription factor that has been implicated in pathways critical to carcinogenesis. Controversy persists as to whether it functions as a tumor suppressor or as an oncogene. WWP1 was amplified and overexpressed in some cancer cell lines and negatively regulated the function of KLF5. WWP1 negatively regulates also the TGFβ signaling by interacting with and degrading multiple components. The present study aims to establish the possible changes of TGFβ, KLF5 and WWP1 gene expression during cervical cancer development and the possible relationship with HPV infection. Quantitative Real Time PCR was used to evaluate the expression level of target genes. HPV DNA was detected and genotyped using Linear Array HPV Genotyping Test. Data were statistically analyzed using the Kruskal-Wallis test. The genotypes most present were high-risk HPV 66, 31, 33, 16 and 18 single or in co-infections. TGFβ expression level increased in CIN II-III lesions and tumors. KLF5 gene expression was down-regulated especially in SCC. Expression of WWP1 gene was increased in SCC and CIN II-III and was significant higher in HPV negative samples, suggesting that the carcinogenesis mediated by this factor is independent of HPV infection (p=0.0023). All three investigated genes suffer changes in gene expression level suggesting the possibility to use them in the future for disease management.
Keywords: cervical cancer,HPV,tumor growth factor-beta,KLF5,WWP1
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Botezatu A, Goia-Ruşanu CD, Stănescu AD, Iancu IV, Popa E, Nistor E, et al. WWP1, TGF β and KLF5 gene expression levels as new possible factors involved in cervical oncogenesis. Rev Romana Med Lab. 2011;19(1):47-54
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