Invasion activating caveolin-1 mutation in human scirrhous breast cancers.
We looked for mutations in the caveolin-1 gene, encoding a critical molecule for membrane signaling to cell growth, in 92 primary human breast cancers, and we report here the identification of a mutation in caveolin-1 at codon 132 (P132L) in 16% of cases. The mutation-positive cases were mostly invasive scirrhous carcinomas. In cell lines expressing the same mutant of caveolin-1, we observed that the mutant Caveolin-1 expression seemed to induce cellular transformation and activation of mitogen-activated protein kinase-signaling pathway and to promote invasion-ability as well as altered actin networks in the cells. These results provide, for the first time, genetic evidence that a functioning Caveolin-1 mutation may have a role in the malignant progression of human breast cancer.
Hayashi
K
K
Department of Molecular Pathogenesis, Nagoya University School of Medicine, Japan.
Matsuda
S
S
Machida
K
K
Yamamoto
T
T
Fukuda
Y
Y
Nimura
Y
Y
Hayakawa
T
T
Hamaguchi
M
M
D016475:3T3 Cells; D002293:Adenocarcinoma, Scirrhous / Q000235:genetics* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D003062:Codon; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017386:Sequence Homology, Amino Acid
C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D003062:Codon