E6/E7 of HPV type 16 promotes cell invasion and metastasis of human breast cancer cells.
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 upregulation 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 overexpression 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.
Yasmeen
Amber
A
Program in Cancer Genetics, Oncology Department, McGill University, Montreal, Quebec, Canada.
Bismar
Tarek A
TA
Kandouz
Mustapha
M
Foulkes
William D
WD
Desprez
Pierre-Yves
PY
Al Moustafa
Ala-Eddin
AE
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009361:Neoplasm Invasiveness; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014183:Transplantation, Heterologous
C068651:E6 protein, Human papillomavirus type 16; C497453:ID1 protein, human; C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16