The N-terminal domain of SV40 large T antigen represses the HER2/neu-mediated transformation and metastatic potential in breast cancers

HER2/neu is known to be overexpressed in approximately 40% of human breast and ovarian cancers and it is associated with increased metastasis and poor prognosis. We have shown previously that the N-terminal domain of simian virus 40 large T antigen (LT425) can act as a transforming suppressor of the...

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Bibliographic Details
Published in:FEBS letters 2002-01, Vol.511 (1), p.46-50
Main Authors: Chuang, Tzu-Chao, Yu, Yuh-Hua, Lin, Yen-Shing, Wang, Shan-Shue, Kao, Ming-Ching
Format: Article
Language:English
Subjects:
Antigens, Polyomavirus Transforming - chemistry
Antigens, Polyomavirus Transforming - genetics
Antigens, Polyomavirus Transforming - metabolism
Blotting, Western
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Breast Neoplasms - pathology
Cell Division
Cell Transformation, Neoplastic - genetics
Cell Transformation, Neoplastic - metabolism
Cell Transformation, Neoplastic - pathology
Chemotaxis
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Genes, erbB-2 - genetics
HER2/neu
Humans
Metastasis
Neoplasm Metastasis - genetics
Neoplasm Metastasis - pathology
p185
Protein Structure, Tertiary
Receptor, ErbB-2 - antagonists & inhibitors
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - metabolism
Simian virus 40 large T antigen
Tumor Cells, Cultured
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Summary:HER2/neu is known to be overexpressed in approximately 40% of human breast and ovarian cancers and it is associated with increased metastasis and poor prognosis. We have shown previously that the N-terminal domain of simian virus 40 large T antigen (LT425) can act as a transforming suppressor of the HER2/ neu oncogene in human ovarian cancer. In the present study, we demonstrate that LT425 can also repress the transforming properties of HER2/neu-overexpressing human breast cancer cells. In addition, the results of a chemotaxis assay and an in vitro chemoinvasion assay further suggest that LT425 can also suppress the metastatic potential of the HER2/neu-transformed breast cancer cells. Taken together, these data clearly suggest that the inhibition of the expression of p185 HER2/neu tyrosine kinase by LT425 is capable of suppressing the HER2/neu-mediated transformation and metastatic potential in breast cancers.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(01)03277-X