This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jackson, J. G. Articles by Yee, D. Search for Related Content PubMed PubMed Citation Articles by Jackson, J. G. Articles by Yee, D.

Elevated Levels of p66 Shc Are Found in Breast Cancer Cell Lines and Primary Tumors with High Metastatic Potential¹

Divisions of Medical Oncology [J. G. J., G. M. C., D. Y.] and Endocrinology [T. Y.], Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7884

The adapter molecule Shc has been implicated in specific steps of metastasis. In the current study, we show that the expression and activation of the p66 Shc isoform increased in a highly metastatic variant (F-11) of the human breast cancer cell line MDA-MB-231 compared to the parent cell line, whereas the p46 and p52 Shc isoforms were unchanged. Despite reports that p66 Shc can negatively regulate epidermal growth factor signaling to the mitogen-activated protein kinase pathway, we found no change in epidermal growth factor-stimulated activation of mitogen-activated protein kinase in the F-11 cell line. We determined the level of Shc expression by immunoblot in primary breast cancer specimens obtained from patients with or without axillary node involvement. p66 Shc expression increased in tumors obtained from node-positive patients (Spearman correlation coefficient = 0.43377; P = 0.0058) compared to the node-negative specimens. Furthermore, increasing levels of p66 Shc correlated with an increasing number of positive nodes (P = 0.032). This study shows that p66 Shc expression increased in cultured breast cancer cells selected for metastasis and in primary human breast cancer specimens obtained from patients with lymph node involvement, suggesting a possible role for Shc in human breast cancer metastasis.

This article has been cited by other articles:

				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]

				G. Xi, X. Shen, and D. R. Clemmons p66shc Negatively Regulates Insulin-Like Growth Factor I Signal Transduction via Inhibition of p52shc Binding to Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate-1 Leading to Impaired Growth Factor Receptor-Bound Protein-2 Membrane Recruitment Mol. Endocrinol., September 1, 2008; 22(9): 2162 - 2175. [Abstract] [Full Text] [PDF]

				A. Chahdi and A. Sorokin Endothelin-1 Couples {beta}Pix to p66Shc: Role of {beta}Pix in Cell Proliferation through FOXO3a Phosphorylation and p27kip1 Down-Regulation Independently of Akt Mol. Biol. Cell, June 1, 2008; 19(6): 2609 - 2619. [Abstract] [Full Text] [PDF]

				M. Gertz, F. Fischer, D. Wolters, and C. Steegborn Activation of the lifespan regulator p66Shc through reversible disulfide bond formation PNAS, April 15, 2008; 105(15): 5705 - 5709. [Abstract] [Full Text] [PDF]

				P. Sansone, G. Storci, C. Giovannini, S. Pandolfi, S. Pianetti, M. Taffurelli, D. Santini, C. Ceccarelli, P. Chieco, and M. Bonafe p66Shc/Notch-3 Interplay Controls Self-Renewal and Hypoxia Survival in Human Stem/Progenitor Cells of the Mammary Gland Expanded In Vitro as Mammospheres Stem Cells, March 1, 2007; 25(3): 807 - 815. [Abstract] [Full Text] [PDF]

				S. Hiscox, L Morgan, T. Green, and R. I Nicholson Src as a therapeutic target in anti-hormone/anti-growth factor-resistant breast cancer Endocr. Relat. Cancer, December 1, 2006; 13(Supplement_1): S53 - S59. [Abstract] [Full Text] [PDF]

				S. De, O. Razorenova, N. P. McCabe, T. O'Toole, J. Qin, and T. V. Byzova VEGF-integrin interplay controls tumor growth and vascularization PNAS, May 24, 2005; 102(21): 7589 - 7594. [Abstract] [Full Text] [PDF]

				G. Loughran, N. C. Healy, P. A. Kiely, M. Huigsloot, N. L. Kedersha, and R. O'Connor Mystique Is a New Insulin-like Growth Factor-I-regulated PDZ-LIM Domain Protein That Promotes Cell Attachment and Migration and Suppresses Anchorage-independent Growth Mol. Biol. Cell, April 1, 2005; 16(4): 1811 - 1822. [Abstract] [Full Text] [PDF]

				U. Sivaprasad, J. Fleming, P. S. Verma, K. A. Hogan, G. Desury, and W. S. Cohick Stimulation of Insulin-Like Growth Factor (IGF) Binding Protein-3 Synthesis by IGF-I and Transforming Growth Factor-{alpha} Is Mediated by Both Phosphatidylinositol-3 Kinase and Mitogen-Activated Protein Kinase Pathways in Mammary Epithelial Cells Endocrinology, September 1, 2004; 145(9): 4213 - 4221. [Abstract] [Full Text] [PDF]

				A. Ventura, L. Luzi, S. Pacini, C. T. Baldari, and P. G. Pelicci The p66Shc Longevity Gene Is Silenced through Epigenetic Modifications of an Alternative Promoter J. Biol. Chem., June 14, 2002; 277(25): 22370 - 22376. [Abstract] [Full Text] [PDF]