UVB irradiation down-regulates HPV-16 RNA expression: Implications for malignant progression of transformed cells

Abstract

A new cell line obtained from normal human epithelial keratinocytes transfected with the whole HPV-16 genome has been extensively characterised. This cell line, named HK-168, has a basal/para-basal keratinocyte phenotype, requires the use of serum-free chemically defined media and maintains the ability to differentiate toward pluri-stratified epithelia. Although immortalised it is not capable of anchorage independent growth and is not tumorigenic. HK-168 has a distinctive kariotype, with a complete, transcriptionally active HPV-16 genome integrated at an almost 1:1 ratio into the host haploid genome thus providing a convenient experimental model for viral transformed pre-neoplastic cell phenotype. The oxidative stress, induced by mild UVB irradiation, caused in HK-168 a general suppression of viral transcription, accompanied by a moderate growth arrest, an appropriated response of cellular antioxidant enzymes, the activation of cell repair mechanisms and a mild induction of apoptosis. This response is similar to the one observed in the highly resistant diploid keratinocytes. Conversely, transformed cells devoid of HPV sequences (HaCaT), appeared extremely susceptible to apoptosis. We propose that reported suppression of viral oncogenes, restoring the cell control on growth and repair mechanisms, allows the damage repair, ultimately resulting in a surviving response.