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 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.
Chuang
Tzu-Chao
TC
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
Yu
Yuh-Hua
YH
Lin
Yen-Shing
YS
Wang
Shan-Shue
SS
Kao
Ming-Ching
MC
D000952:Antigens, Polyomavirus Transforming / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002633:Chemotaxis; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2 / Q000235:genetics*; D006801:Humans; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000952:Antigens, Polyomavirus Transforming; D018719:Erb-b2 Receptor Tyrosine Kinases