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Brief Report

ErbB-2 Receptor Cooperates with E6/E7 Oncoproteins of HPV Type 16 in Breast Tumorigenesis

Amber Yasmeen, Tarek A. Bismar, Hafedh Dekhil, Riccardo Ricciardi, Amal Kassab, Carlo Gambacorti-Passerini and Ala-Eddin Al Moustafa

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The ErbB-2 receptor is overexpressed in roughly 30% of human breast cancers. Moreover, approximately 50% of breast cancers are positive for high-risk human papillomaviruses (HPVs), specifically types 16 and 18. Recently, we reported that ErbB-2 cooperates with E6/E7 oncoproteins of HPV type 16 to induce neoplastic transformation of human normal oral epithelial cells. We also demonstrated that E6/E7 of HPV type 16 converts non-invasive breast cancer cells to an invasive form. In order to investigate the effect of ErbB-2/E6/E7 cooperation in breast carcinogenesis, we generated double transgenic mice carrying ErbB-2 and E6/E7 of HPV type 16 under mouse mammary tumor virus (MMTV) and human keratin 14 promoters, respectively. Within six months, these double transgenic mice developed large and extensive invasive breast cancer in comparison to ErbB-2 or E6/E7 singly transgenic mice. Histological analysis of ErbB-2/E6/E7 transgenic mice tumors showed the presence of invasive breast carcinomas. However, the breast tissues from ErbB-2 and E6/E7 transgenic mice showed only in-situ cancer and normal mammary phenotype, respectively. In parallel, we examined the cooperation effect of ErbB-2 and E6/E7 in the human breast cancer cell line, BT20; in comparison to ErbB-2 and E6/E7 alone as well as wild type cells, we found that ErbB 2/E6/E7 together stimulate colony formation and cell migration in the BT20 cell line. Furthermore, we found that β-catenin is constitutively phosphorylated by c-Src and consequently trans-located to the nucleus in ErbB-2/E6/E7-breast cancer cells. These findings provide evidence that the ErbB-2 receptor cooperates with high-risk HPVs in breast tumorigenesis via β-catenin activation.

Authors

Amber Yasmeen

McGill University; Montreal, Quebec, Canada

Tarek A. Bismar

McGill University; Montreal, Quebec, Canada

Hafedh Dekhil

McGill University; Montreal, Quebec Canada

Riccardo Ricciardi

McGill University; Montreal, Quebec Canada

Amal Kassab

McGill University; Montreal, Quebec Canada

Carlo Gambacorti-Passerini

McGill University; Montreal, Quebec Canada

Ala-Eddin Al Moustafa

McGill University; Montreal, Quebec, Canada

Purchase article for $19

Subscribe to this journal for $129/year