Oncogenic Human Papillomaviruses Activate the Tumor-Associated Lens Epithelial-Derived Growth Factor (LEDGF) Gene

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Specific types of human papillomaviruses (HPVs) are closely linked to the development of malignant tumors, such as cervical cancer. Virtually all cervical cancers contain HPV DNA and the tumorigenic growth behavior of cervical cancer cells is dependent on the activity of two viral oncogenes, called E6 and E7. It is important to study the activities by which the HPV oncogenes can support the growth of tumor cells. This should allow new insights into the molecular mechanisms of virus-induced carcinogenesis and could also be useful for developing novel approaches for cancer therapy. We here show that the HPV oncogenes stimulate and maintain expression of the cellular LEDGF gene in HPV-positive cancer cells. Consistently, pre-malignant and malignant lesions of the cervix exhibit significantly increased LEDGF protein levels. LEDGF is crucial for the protection of tumor cells against various forms of cellular stress, including DNA damage. LEDGF stimulation by the viral oncogenes could be a critical survival mechanism by which HPVs support the growth of cervical cancer cells and provide resistance towards chemo- and radiotherapy in the clinic.

Vyšlo v časopise: Oncogenic Human Papillomaviruses Activate the Tumor-Associated Lens Epithelial-Derived Growth Factor (LEDGF) Gene. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003957
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003957

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