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Aberrant expression and activation of insulin-like growth factor-1 receptor (IGF-1R) are mediated by an induction of IGF-1R promoter activity and stabilization of IGF-1R mRNA and contributes to growth factor independence and increased survival of the pancreatic cancer cell line MIA PaCa-2.
Oncogene 2001; 20(57):8203-14O

Abstract

In the present study we investigated the mechanisms responsible for and the biological consequences of the constitutive activation of the insulin-like growth factor-1 receptor (IGF-1R) in the MIA PaCa-2 cells. An aberrant increase in the expression and activation of the IGF-1R was observed during the transition of growth states from exponential to quiescent. The increase in IGF-1R expression is preceded by an increase in IGF-1R mRNA transcript and is associated with an increase in the IGF-1R promoter activity. Inhibition of de novo transcription by actinomycin D increased the stability of IGF-1R mRNA in exponentially growing cells, thereby increasing the expression of IGF-1R to a level similar to that seen in quiescent cells. Increased IGF-1R signaling mediated the growth factor independence of quiescent MIA PaCa-2 cells through the constitutive activation of mitogen-activated protein kinase (MAPK). Exogenous IGF-1 increased cell proliferation and activated MAPK and AKT signaling pathways. The resistance of cells to apoptosis by IGF-1R signaling was mediated through MAPK and phosphatidylinositol 3-kinase (PI3K) pathways and a yet unidentified pathway(s). Thus, aberrant regulation of IGF-1R signaling is required for resistance to apoptosis and growth factor independence of MIA PaCa-2 cells. This likely protects cells from unfavorable conditions and allows cells to rapidly re-enter the cell cycle when conditions are favorable.

Authors+Show Affiliations

Department of Surgery, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11781836

Citation

Nair, P N., et al. "Aberrant Expression and Activation of Insulin-like Growth Factor-1 Receptor (IGF-1R) Are Mediated By an Induction of IGF-1R Promoter Activity and Stabilization of IGF-1R mRNA and Contributes to Growth Factor Independence and Increased Survival of the Pancreatic Cancer Cell Line MIA PaCa-2." Oncogene, vol. 20, no. 57, 2001, pp. 8203-14.
Nair PN, De Armond DT, Adamo ML, et al. Aberrant expression and activation of insulin-like growth factor-1 receptor (IGF-1R) are mediated by an induction of IGF-1R promoter activity and stabilization of IGF-1R mRNA and contributes to growth factor independence and increased survival of the pancreatic cancer cell line MIA PaCa-2. Oncogene. 2001;20(57):8203-14.
Nair, P. N., De Armond, D. T., Adamo, M. L., Strodel, W. E., & Freeman, J. W. (2001). Aberrant expression and activation of insulin-like growth factor-1 receptor (IGF-1R) are mediated by an induction of IGF-1R promoter activity and stabilization of IGF-1R mRNA and contributes to growth factor independence and increased survival of the pancreatic cancer cell line MIA PaCa-2. Oncogene, 20(57), pp. 8203-14.
Nair PN, et al. Aberrant Expression and Activation of Insulin-like Growth Factor-1 Receptor (IGF-1R) Are Mediated By an Induction of IGF-1R Promoter Activity and Stabilization of IGF-1R mRNA and Contributes to Growth Factor Independence and Increased Survival of the Pancreatic Cancer Cell Line MIA PaCa-2. Oncogene. 2001 Dec 13;20(57):8203-14. PubMed PMID: 11781836.
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TY - JOUR T1 - Aberrant expression and activation of insulin-like growth factor-1 receptor (IGF-1R) are mediated by an induction of IGF-1R promoter activity and stabilization of IGF-1R mRNA and contributes to growth factor independence and increased survival of the pancreatic cancer cell line MIA PaCa-2. AU - Nair,P N, AU - De Armond,D T, AU - Adamo,M L, AU - Strodel,W E, AU - Freeman,J W, PY - 2001/04/03/received PY - 2001/10/04/revised PY - 2001/10/09/accepted PY - 2002/1/10/pubmed PY - 2002/1/24/medline PY - 2002/1/10/entrez SP - 8203 EP - 14 JF - Oncogene JO - Oncogene VL - 20 IS - 57 N2 - In the present study we investigated the mechanisms responsible for and the biological consequences of the constitutive activation of the insulin-like growth factor-1 receptor (IGF-1R) in the MIA PaCa-2 cells. An aberrant increase in the expression and activation of the IGF-1R was observed during the transition of growth states from exponential to quiescent. The increase in IGF-1R expression is preceded by an increase in IGF-1R mRNA transcript and is associated with an increase in the IGF-1R promoter activity. Inhibition of de novo transcription by actinomycin D increased the stability of IGF-1R mRNA in exponentially growing cells, thereby increasing the expression of IGF-1R to a level similar to that seen in quiescent cells. Increased IGF-1R signaling mediated the growth factor independence of quiescent MIA PaCa-2 cells through the constitutive activation of mitogen-activated protein kinase (MAPK). Exogenous IGF-1 increased cell proliferation and activated MAPK and AKT signaling pathways. The resistance of cells to apoptosis by IGF-1R signaling was mediated through MAPK and phosphatidylinositol 3-kinase (PI3K) pathways and a yet unidentified pathway(s). Thus, aberrant regulation of IGF-1R signaling is required for resistance to apoptosis and growth factor independence of MIA PaCa-2 cells. This likely protects cells from unfavorable conditions and allows cells to rapidly re-enter the cell cycle when conditions are favorable. SN - 0950-9232 UR - https://www.unboundmedicine.com/medline/citation/11781836/Aberrant_expression_and_activation_of_insulin_like_growth_factor_1_receptor__IGF_1R__are_mediated_by_an_induction_of_IGF_1R_promoter_activity_and_stabilization_of_IGF_1R_mRNA_and_contributes_to_growth_factor_independence_and_increased_survival_of_the_pancreatic_cancer_cell_line_MIA_PaCa_2_ L2 - http://dx.doi.org/10.1038/sj.onc.1205044 DB - PRIME DP - Unbound Medicine ER -