Send to

Choose Destination
Anticancer Res. 2003 Mar-Apr;23(2B):1517-24.

Insulin-like growth factor 1 receptor activates c-SRC and modifies transformation and motility of colon cancer in vitro.

Author information

Department of Interdisciplinary Oncology, Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612-9497, USA.


Colorectal carcinomas have been found to express increased levels of IGF1 and IGF1-R, as compared to normal or adenomatous colonic mucosa, and it has been postulated that a subset of colorectal cancers are under the autocrine regulation of the IGF1/IGF1-R system. In this study, we selected human colorectal carcinoma cell lines with high (SW620, HT29, L4A) and low (CaCo2, and HCT 116) expression of IGF1-R by flow cytometry. Compared to the IGF1-R(-) cells, the IGF1-R(+) cells revealed a more aggressive phenotype as demonstrated by a higher proliferation rate (approximately 2-fold increase) in response to IGF1, higher degree of transformation (approximately 5-to-15-fold increase in colony formation in soft agar), increased resistance to serum deprivation-induced apoptosis [1-7 apoptotic cells/5 microscopic fields, as compared to 37 to 101 apoptotic cells/5 microscopic fields of the IGF1-R(-) cells], and higher migratory capability measured by a wounding assay [IGF1-R(+) cells migrated a distance of up to 15 millimeters from the cut edge of the monolayer, while the IGF1-R(-) cells were able to migrate only 2-3 millimeters away from the same reference point]. While the cell lines overexpressing the IGF1-R had higher levels of Src activation, the use of a Src inhibitor reduced the IGF1-R protein expression, slowed down the proliferation of IGF1-R(+) cells, and reduced their colony formation in soft agar. Based on the above observations, we conclude that an overexpressed and activated IGF1-R may increase the degree of transformation and motility of colon cancer cells by activating c-Src.

[Indexed for MEDLINE]

Supplemental Content

Loading ...
Support Center