HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, J.-L. Articles by LeRoith, D. Search for Related Content PubMed PubMed Citation Articles by Liu, J.-L. Articles by LeRoith, D. Social Bookmarking                      What's this?

Volume 272, Number 47, Issue of November 21, 1997 pp. 29438-29441
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

COMMUNICATION:
The Constitutively Active Mutant G₁₃ Transforms Mouse Fibroblast Cells Deficient in Insulin-like Growth Factor-I Receptor

(Received for publication, March 13, 1997, and in revised form, October 12, 1997)

From the Section on Cellular and Molecular Physiology, Diabetes Branch, NIDDK and the ^§ Laboratory of Cellular Development and Oncology, NIDR, National Institutes of Health, Bethesda, Maryland 20892

Insulin-like growth factor-I (IGF-I) receptor plays an important role in normal cell cycle progression and tumor growth, and it is thought to be essential for cellular transformation. To test this hypothesis, we stably transfected a GTPase-deficient mutant human G₁₃, which is highly oncogenic when overexpressed in vitro, into R fibroblasts derived from IGF-I receptor-deficient mice. Northern blots of multiple clones revealed the expression of a 1.8-kilobase pair mutant G₁₃ transcript in transfected cells, in addition to the 6-kilobase pair endogenous mRNA. The transfection resulted in a doubling of the expression of G₁₃ protein in these cells as assessed by Western blot analysis. The transforming ability of the mutant G₁₃ was tested using the soft agar assay. Nontransfected R cells cultured with 10% fetal bovine serum failed to form colonies after 3 weeks. Most of the mutant G₁₃-expressing clones formed significant numbers of colonies (11-50 colonies/1000 cells plated). Overexpression of the IGF-I receptor enabled R cells to form colonies (27 colonies), and co-transfection of the mutant G₁₃ caused a further increase in colony formation (117-153 colonies) in three of five clones analyzed. Apparently G₁₃ works through pathways other than mitogen-activated protein kinase and c-Jun N-terminal kinase in transforming R cells, because their activities were not significantly altered by the mutant G₁₃ expression. These results demonstrate that G₁₃ can induce cellular transformation through pathways apparently independent of the IGF-I receptor and that activation of the IGF-I receptor signaling pathways, although not essential for the transforming phenotype, enhances the effect of other pathways.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Sachdev and D. Yee Disrupting Insulin-Like Growth Factor Signaling as a Potential Cancer Therapy Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 39 - 58. [Abstract] [Full Text] [PDF]

				D. Sachdev and D. Yee Disrupting insulin-like growth factor signaling as a potential cancer therapy Mol. Cancer Ther., January 1, 2007; 6(1): 1 - 12. [Abstract] [Full Text] [PDF]

				S. L. Spence, A. L. Shaffer, L. M. Staudt, S. Amde, S. Manney, C. Terry, K. Weisz, and P. Nissley Transformation of Late Passage Insulin-Like Growth Factor-I Receptor Null Mouse Embryo Fibroblasts by SV40 T Antigen. Cancer Res., April 15, 2006; 66(8): 4233 - 4239. [Abstract] [Full Text] [PDF]

				Y. Zhang, M. Karas, H. Zhao, S. Yakar, and D. LeRoith 14-3-3{sigma} Mediation of Cell Cycle Progression Is p53-independent in Response to Insulin-like Growth Factor-I Receptor Activation J. Biol. Chem., August 13, 2004; 279(33): 34353 - 34360. [Abstract] [Full Text] [PDF]

				J. Tao, C. C. Malbon, and H.-y. Wang Galpha i2 Enhances Insulin Signaling via Suppression of Protein-tyrosine Phosphatase 1B J. Biol. Chem., October 19, 2001; 276(43): 39705 - 39712. [Abstract] [Full Text] [PDF]

				B Valentinis and R Baserga IGF-I receptor signalling in transformation and differentiation Mol. Pathol., June 1, 2001; 54(3): 133 - 137. [Abstract] [Full Text]

				H. Hallak, A. E. M. Seiler, J. S. Green, B. N. Ross, and R. Rubin Association of Heterotrimeric Gi with the Insulin-like Growth Factor-I Receptor. RELEASE OF Gbeta gamma SUBUNITS UPON RECEPTOR ACTIVATION J. Biol. Chem., January 28, 2000; 275(4): 2255 - 2258. [Abstract] [Full Text] [PDF]