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Reports

E6/E7 of HPV Type 16 Promotes Cell Invasion and Metastasis of Human Breast Cancer Cells

Amber Yasmeen, Tarek A. Bismar, Mustapha Kandouz, William D. Foulkes, Pierre-Yves Desprez and Ala-Eddin Al Moustafa

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Human papillomaviruses (HPVs) could be important risk factors for breast carcinogenesis and metastasis, as roughly 50% of breast cancers are positive for high-risk HPVs. To determine the role of high-risk HPVs in human breast carcinogenesis and metastasis, we examined the effect of E6/E7 of HPV type 16 in two non-invasive breast cancer cell lines, MCF7 and BT20. We report that E6/E7 of HPV type 16 induces cell invasive and metastatic abilities of MCF7 and BT20 in vitro and in vivo, respectively, in comparison with the wild type cells. This is accompanied by an up-regulation of Id-1, a family member of helix-loop-helix (HLH) transcription factors, in MCF7 and BT20 cell lines which express E6/E7. Earlier studies have reported that Id-1 regulates cell invasion and metastasis of human breast cancer cells. To gauge the role of Id-1 in cell invasion and metastasis induced by E6/E7 of HPV type 16, we investigated the effect of E6/E7 in mouse normal embryonic fibroblast (NEF) and knockout Id-1 (Id-1-/-) cells. We establish that E6/E7 induces cell invasive ability in NEF but not Id-1-/- cells; moreover, we were able to inhibit the invasion ability of MCF7-E6/E7 and BT20-E6/E7 using Id-1 antisense retroviruses. Furthermore, we report that E6/E7 oncoproteins up-regulate Id-1 promoter activity in MCF7 and BT20 cells. We also found that HPV type 16 is present in all invasive and metastatic breast cancer and less frequently in in-situ breast cancer as opposed to normal mammary tissue. In parallel, we demonstrate that Id-1 over-expression is correlated with the presence of HPV type 16 in human invasive and metastatic breast cancer. These data suggest that high-risk HPV infections can induce cell invasion and metastasis in breast cancer through Id-1 regulation.

Authors

Amber Yasmeen

McGill University; Montreal, Quebec, Canada

Tarek A. Bismar

McGill University; Montreal, Quebec, Canada

Mustapha Kandouz

Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital; Montreal, Quebec, Canada

William D. Foulkes

McGill University; Montreal, Quebec, Canada

Pierre-Yves Desprez

California Pacific Medical Center Research Institute; San Francisco, California

Ala-Eddin Al Moustafa

McGill University; Montreal, Quebec, Canada

Purchase article for $19

Subscribe to this journal for $129/year