Requirement of different signaling pathways mediated by insulin-like growth factor-I receptor for proliferation, invasion, and VPF/VEGF expression in a pancreatic carcinoma cell line.
Several oncogenes and growth factors are found to be mutated and overexpressed in adenocarcinoma of the pancreas, and may correlate with its highly aggressive nature. Insulin-like growth factor (IGF-I) and its receptor (IGF-IR) are highly expressed in this tumor type. We examined the IGF-IR-mediated signaling pathways in relation to cell proliferation, invasiveness, and expression pattern of vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) in the pancreatic cancer line ASPC-1. Our findings show that IGF-IR is an important growth factor receptor for cell proliferation and invasion, and VPF/VEGF expression in ASPC-1. Further experiments indicate that IGF-IR mediates different signaling pathways to execute its functions. Activation of Ras by IGF-IR was found to be required for the cell invasion. On the other hand Src activation through IGF-IR is required for the cell proliferation, invasion, and also VPF/VEGF expression. Taken together, our data indicate the importance of IGF-IR in growth and invasiveness of the pancreatic cancer cell lines and also point out the multiple signaling pathways channeled through this receptor.
Zeng
Huiyan
H
Department of Pathology, RN270H, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA.
Datta
Kaustubh
K
Neid
Matthias
M
Li
Jinping
J
Parangi
Sareh
S
Mukhopadhyay
Debabrata
D
D001483:Base Sequence; D002455:Cell Division / Q000502:physiology*; D017931:DNA Primers; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D018631:ras Proteins / Q000378:metabolism
D017931:DNA Primers; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017526:Receptor, IGF Type 1; D016392:Proto-Oncogene Proteins pp60(c-src); D018631:ras Proteins