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Insulin-like growth factor 1 receptor enhances invasion and induces resistance to apoptosis of colon cancer cells through the Akt/Bcl-x(L) pathway.
- Source :
-
Cancer research [Cancer Res] 2003 Nov 15; Vol. 63 (22), pp. 7708-16. - Publication Year :
- 2003
-
Abstract
- Colon cancer overexpresses insulin-like growth factor 1 (IGF1) and insulin-like growth factor 1 receptor (IGF1-R), as compared with normal or adenomatous mucosa, and it has been postulated that colorectal cancer cells depend on the IGF1/IGF1-R pathway for their growth and progression. In this study, using the human colon cancer cell line HCT116, we find that established HCT116/IGF1-R transfectants exhibit a more aggressive transformed phenotype than the parental cell line, as demonstrated by their higher proliferation rate in response to IGF1, higher degree of anchorage-independent growth, resistance to serum deprivation-induced apoptosis, and higher migratory capability in a monolayer "wounding assay." When injected into nude mice, HCT116/IGF1-R transfectants were highly invasive and produced distant metastases, whereas the parental cell did not. Moreover, the overexpression of IGF1-R in these cells was associated with IGF1-R-induced activation of Akt and up-regulation of the antiapoptotic protein Bcl-x(L). We also show that Akt pathway mediates IGF1-R-induced Bcl-x(L) expression at transcriptional level. Our data demonstrate, for the first time, that IGF1-R/Akt/Bcl-x(L) pathway may contribute to a more aggressive malignant phenotype, in a subset of colorectal cancers.
- Subjects :
- Animals
Cell Division physiology
Cell Movement physiology
Cell Transformation, Neoplastic genetics
Cell Transformation, Neoplastic metabolism
Colonic Neoplasms genetics
Colonic Neoplasms metabolism
Gene Expression Regulation, Neoplastic
HCT116 Cells
Humans
Mice
Mice, Nude
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Transplantation
Promoter Regions, Genetic
Proto-Oncogene Proteins biosynthesis
Proto-Oncogene Proteins c-akt
Proto-Oncogene Proteins c-bcl-2 biosynthesis
Proto-Oncogene Proteins c-bcl-2 genetics
Receptor, IGF Type 1 biosynthesis
Receptor, IGF Type 1 genetics
Transfection
Transplantation, Heterologous
bcl-X Protein
Apoptosis physiology
Colonic Neoplasms pathology
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins metabolism
Proto-Oncogene Proteins c-bcl-2 metabolism
Receptor, IGF Type 1 physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-5472
- Volume :
- 63
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 14633695