Abstract
To date, the major role of HPV16E6 in cancer has been considered to be its ability to inhibit the p53 tumor-suppressor protein, thereby thwarting p53-mediated cytotoxic responses to cellular stress signals. Here, we show that HPV16E6-dependent c-fos oncogenic protein expression contributes to AP-1 complex formation under oxidative stress in SiHa cells (HPV16-positive squamous cell carcinoma of the cervix). In addition, we examined the role of HPV16E6 in TGF-α-induced c-fos expression and found that the c-fos protein expression induced by TGF-α is HPV16E6 dependent. Thus, our results provide the first evidence that HPV16E6 contributes to AP-1 complex formation after both ligand-dependent and independent EGFR activation, suggesting a new therapeutic approach to the treatment of HPV-associated tumors.
MeSH terms
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Cell Line, Tumor
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Female
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Gene Expression Regulation, Neoplastic
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Humans
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / metabolism*
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / metabolism*
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism*
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Transforming Growth Factor alpha / metabolism
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Uterine Cervical Neoplasms / metabolism
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Uterine Cervical Neoplasms / pathology
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Uterine Cervical Neoplasms / virology
Substances
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E6 protein, Human papillomavirus type 16
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Oncogene Proteins, Viral
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Proto-Oncogene Proteins c-fos
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RNA, Small Interfering
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Repressor Proteins
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Transcription Factor AP-1
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Transforming Growth Factor alpha