TY - JOUR
T1 - 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
AU - Zeng, Huiyan
AU - Datta, Kaustubh
AU - Neid, Matthias
AU - Li, Jinping
AU - Parangi, Sareh
AU - Mukhopadhyay, Debabrata
N1 - Funding Information:
This work was partly supported by American Cancer Society (RSG-01-148-01-CSM) and NIH grant CA78383 (to D.M.). H.Z. is a NRSA Fellow. S.P. is a Medical Foundation/Dolphin Trust fellow. D.M. is a Eugene P. Schonfeld National Kidney Cancer Association Medical Research Awardee.
PY - 2003/2/28
Y1 - 2003/2/28
N2 - 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.
AB - 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.
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U2 - 10.1016/S0006-291X(03)00107-4
DO - 10.1016/S0006-291X(03)00107-4
M3 - Article
C2 - 12593846
AN - SCOPUS:0037470435
SN - 0006-291X
VL - 302
SP - 46
EP - 55
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -