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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
2008-1-4
pubmed:abstractText
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 beta-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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1551-4005
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2939-43
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
ErbB-2 receptor cooperates with E6/E7 oncoproteins of HPV type 16 in breast tumorigenesis.
pubmed:affiliation
Montreal Center for Experimental Therapeutics in Cancer, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec H3T 1E2 Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't