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Old 12-27-2007, 11:09 AM   #1
Lani
Senior Member
 
Join Date: Mar 2006
Posts: 4,778
does her2 gene amplifcn combine with oncoproteins from HPV infection 2 cause her2 BC?

Will HPV vaccination be responsible for a decrease of her2+ bc in the future? Just questions to wonder about...

Cell Cycle. 2007 Aug 30;6(23) [Epub ahead of print]Links
ErbB-2 Receptor Cooperates with E6/E7 Oncoproteins of HPV Type 16 in Breast Tumorigenesis.

Yasmeen A, Bismar TA, Dekhil H, Ricciardi R, Kassab A, Gambacorti-Passerini C, Al Moustafa AE.
Montreal Center for Experimental Therapeutics in Cancer, Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, Jewish General Hospital, McGill University, Montreal, Quebec, Canada; Program in Cancer Genetics, Department of Oncology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
The ErbB-2 receptor is over-expressed in roughly 30% of human breast cancers. Moreover, approximately 50% of breast cancers are positive for high-risk human papillomaviruses (HPVs). 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 noninvasive 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 b-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 beta-catenin activation.
PMID: 18156804 [PubMed - as supplied by publisher]
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