CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stevenson, L. E.
Right arrow Articles by Frackelton, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stevenson, L. E.
Right arrow Articles by Frackelton, A. R., Jr.
Cell Growth & Differentiation Vol. 10, 61-71, January 1999
© 1999 American Association for Cancer Research

Shc Dominant Negative Disrupts Cell Cycle Progression in Both G0-G1 and G2-M of ErbB2-positive Breast Cancer Cells1

Lisa E. Stevenson, Kodimangalam S. Ravichandran and A. Raymond Frackelton, Jr.2

Departments of Pathology and Laboratory Medicine and Medicine, Brown University, and Roger Williams Medical Center [L. E. S., A. R. F.], Providence, Rhode Island 02908, and Beirne Carter Center for Immunology Research and Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908 [K. S. R.].

The Shc protein helps to transmit signals from receptor and cytoplasmic tyrosine kinases to Ras. We have shown that several breast cancer cell lines (MDA-MB-453, BT-474, MDA-MB-361, and SKBR3), which overexpress the ErbB2 receptor tyrosine kinase, contain constitutively tyrosine phosphorylated Shc. To investigate the role of Shc in these cells, we transfected them with a Shc-Y317F dominant-negative mutant defective in signaling to Ras. The transfectants were unable to form stable colonies, suggesting a critical role for Shc in the proliferation of these cells. In contrast, dominant-negative Shc transfectants of the nontransformed breast epithelial cell line HBL-100 grew normally. Surprisingly, cell cycle analysis of transfected SKBR3 cells suggested that the cells were blocked not only in G0-G1, but also in G2-M. The G2-M block was unexpected because Shc-Y317 is downstream of receptor tyrosine kinases that drive the early events in the cell cycle. Both the G0-G1 and G2-M arrest were rescued by transfection with wild-type Shc or oncogenic Ras 12V. Rescue by Ras suggests that Shc Y317 signals upstream of Ras, and that Shc to Ras effector pathways are involved in G2-M, although confirmation awaits a detailed molecular analysis. Most importantly, this work provides the first evidence for Shc involvement in G2-M.




This article has been cited by other articles:


Home page
J Biol ChemHome page
M. Mlih, L. Host, S. Martin, N. Niederhoffer, L. Monassier, J. Terrand, N. Messaddeq, M. Radke, M. Gotthardt, V. Bruban, et al.
The Src Homology and Collagen A (ShcA) Adaptor Protein Is Required for the Spatial Organization of the Costamere/Z-disk Network during Heart Development
J. Biol. Chem., January 23, 2015; 290(4): 2419 - 2430.
[Abstract] [Full Text] [PDF]


Home page
Endocr Relat CancerHome page
S. M. Alam, M. Rajendran, S. Ouyang, S. Veeramani, L. Zhang, and M.-F. Lin
A novel role of Shc adaptor proteins in steroid hormone-regulated cancers
Endocr. Relat. Cancer, March 1, 2009; 16(1): 1 - 16.
[Abstract] [Full Text] [PDF]


Home page
Clin. Cancer Res.Home page
S. S. Jung, H. S. Park, I. J. Lee, H. Namkoong, S. M. Shin, G. W. Cho, S.-A. Ha, Y. G. Park, Y. S. Lee, J. Ko, et al.
The HCCR Oncoprotein as a Biomarker for Human Breast Cancer
Clin. Cancer Res., November 1, 2005; 11(21): 7700 - 7708.
[Abstract] [Full Text] [PDF]


Home page
J. Virol.Home page
L. B. Baughn and N. Rosenberg
Disruption of the Shc/Grb2 Complex during Abelson Virus Transformation Affects Proliferation, but Not Apoptosis
J. Virol., February 15, 2005; 79(4): 2325 - 2334.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
H. M. Hermanns, S. Radtke, F. Schaper, P. C. Heinrich, and I. Behrmann
Non-redundant Signal Transduction of Interleukin-6-type Cytokines: THE ADAPTER PROTEIN Shc IS SPECIFICALLY RECRUITED TO THE ONCOSTATIN M RECEPTOR
J. Biol. Chem., December 29, 2000; 275(52): 40742 - 40748.
[Abstract] [Full Text] [PDF]


Home page
Cell Growth Differ.Home page
U. Hermanto, C. S. Zong, and L.-H. Wang
Inhibition of Mitogen-activated Protein Kinase Kinase Selectively Inhibits Cell Proliferation in Human Breast Cancer Cells Displaying Enhanced Insulin-like Growth Factor I-mediated Mitogen-activated Protein Kinase Activation
Cell Growth Differ., December 1, 2000; 11(12): 655 - 664.
[Abstract] [Full Text]


Home page
J Biol ChemHome page
H. M. Hermanns, S. Radtke, F. Schaper, P. C. Heinrich, and I. Behrmann
Non-redundant Signal Transduction of Interleukin-6-type Cytokines: THE ADAPTER PROTEIN Shc IS SPECIFICALLY RECRUITED TO THE ONCOSTATIN M RECEPTOR
J. Biol. Chem., December 29, 2000; 275(52): 40742 - 40748.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.