title: Insulin-like growth factor 1 receptor activates c-SRC and modifies transformation and motility of colon cancer in vitro.
abstract: 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.
authors.affiliation: Department of Interdisciplinary Oncology, Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612-9497, USA.
authors.forename: Madhavi
authors.initials: M
authors.lastname: Sekharam
authors.forename: Aejaz
authors.initials: A
authors.lastname: Nasir
authors.forename: Hans E
authors.initials: HE
authors.lastname: Kaiser
authors.forename: Domenico
authors.initials: D
authors.lastname: Coppola
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division; D002465:Cell Movement / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003110:Colonic Neoplasms / Q000473:pathology*; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D018450:Disease Progression; D004790:Enzyme Induction / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D016391:Genes, src; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D011728:Pyridones / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000187:drug effects / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D016895:Culture Media, Serum-Free; D009363:Neoplasm Proteins; D011728:Pyridones; D011743:Pyrimidines; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D019061:src-Family Kinases; C410732:PD 180970