The N-terminal 178-amino-acid domain only of the SV40 large T antigen acts as a transforming suppressor of the HER-2/neu oncogene.
The deregulation of the HER-2/neu protooncogene was demonstrated in a wide variety of human cancers and shown to be correlated with the progress of malignancy and metastasis in animal models. Repression of HER-2/neu overexpression suppressed the malignant phenotypes of HER-2/neu-overexpressing cancer cells. This suggested that HER-2/neu may be a good target for developing anti-cancer drugs. We found a deletion mutant of simian virus 40 (SV40) large T antigen (LT) suppresses the HER-2/neu oncogene expression at the transcriptional level. PCR clones of this mutant SV40LT, named LT425, which contains the N-terminal region of amino acid residues 1-178 of SV40LT, were subcloned and stably transfected into the HER-2/neu-overexpressing human ovarian cancer SKOV3.ip1 cells. These LT425 clones were found to be able to down-regulate the endogenous production of p185(HER-2/neu). In addition, the LT425-expressing stable transfectants showed reduced growth rate, low soft agarose colony forming ability, and low tumorigenic potential as compared with the parental line. These data suggested that the N-terminal 178 amino acids domain only of SV40LT may act as a transforming repressor of HER-2/neu oncogene.
Kao
M C
MC
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan, ROC.
Liu
G Y
GY
Chuang
T C
TC
Lin
Y S
YS
Wuu
J A
JA
Law
S L
SL
D000595:Amino Acid Sequence; D000957:Antigens, Viral, Tumor / Q000737:chemistry / Q000235:genetics*; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D016147:Genes, Tumor Suppressor / Q000235:genetics / Q000502:physiology*; D005822:Genetic Vectors; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000473:pathology
D000957:Antigens, Viral, Tumor; D009363:Neoplasm Proteins; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases