Investigating HPV as a cause for breast cancer

Abstract

HPV is recognized to be causal in cervical and head and neck cancers; its mechanism in malignancy through HPV oncogenes E6 and E7 is well documented. Several studies have found HPV in breast cancer specimens and suggest that HPV may play a contributing role to breast carcinogenesis. Our laboratory had previously identified an HPV-containing breast cancer cell line, MDA-MB-175 VII, which had also been reported to express E6 mRNA (demonstrated by RT-PCR). To investigate the potential causal role for HPV in breast cancer, HPV E6 and E7 expression was inhibited in this HPV-containing breast cancer cell line and the effects of inhibition were quantified by quantitative PCR (qPCR) and Western blot. Measurement of expression levels by qPCR indicated that there was an absence of E6 and E7 expression prior to E6/E7 siRNA treatment. Despite this, however, E6/E7 siRNA treatment resulted in the detection of p53 protein and restoration of p53 activity in MDA-MB-175 VII, corresponding to the effect observed in HPV-transformed HeLa cells. This suggests that HPV is likely to have contributed to the early carcinogenesis of these breast cancer cells but may no longer be required for maintenance of the malignant tumour phenotype.