SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines.

SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines. Research Abstract Details 

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SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines. Abstract Text:

Jie Zhang,Shailaja Kalyankrishna,Marie Wislez,Nishan Thilaganathan,Babita Saigal,Wei Wei,Long Ma,Ignacio I Wistuba,Faye M Johnson,Jonathan M Kurie,

The role of Src-family kinases (SFKs) in non-small cell lung cancer (NSCLC) has not been fully defined. Here we addressed this question by examining SFK phosphorylation in NSCLC biopsy samples and using genetic and pharmacological approaches to inhibit SFK expression and activity in cultured NSCLC cells. Immunohistochemical analysis of NSCLC biopsy samples using a Tyr416 phosphorylation-specific, pan-SFK antibody revealed staining in 123 (33%) of 370 tumors. Because c-Src is known to be both an upstream activator and downstream mediator of epidermal growth factor receptor (EGFR), we next investigated SFK phosphorylation in a panel of NSCLC cell lines, including ones that depend on EGFR for survival. The EGFR-dependent NSCLC cell lines HCC827 and H3255 had increased phosphorylation of SFKs, and treatment of these cells with an SFK inhibitor (PP1 or SKI-606) induced apoptosis. PP1 decreased phosphorylation of EGFR, ErbB2, and ErbB3 and strikingly enhanced apoptosis by gefitinib, an EGFR inhibitor. HCC827 cells transfected with c-Src short hairpin RNA exhibited diminished phosphorylation of EGFR and ErbB2 and decreased sensitivity to apoptosis by PP1 or gefitinib. We conclude that SFKs are activated in NSCLC biopsy samples, promote the survival of EGFR-dependent NSCLC cells, and should be investigated as therapeutic targets in NSCLC patients.

SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines. Publishing Authors By Initials

J Zhang,S Kalyankrishna,M Wislez,N Thilaganathan,B Saigal,W Wei,L Ma,II Wistuba,FM Johnson,JM Kurie,

For similar enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-tyrosine kinases: src-family kinases research abstracts see: enzymes and coenzymes: enzymes: transferases: phosphotransferases: phosphotransferases (alcohol group acceptor): protein kinases: protein-tyrosine kinases: src-family kinases research

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SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: The American journal of pathology

VOLUME: 170

Page Numbers: 366-76

Journal Abbreviation: Am. J. Pathol.

ISSN: 0002-9440

DAY: 3

MONTH: Jan

YEAR: 2007

SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines. Information

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LANGUAGE: eng

NlmUniqueID: 370502

SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines. Keywords Mesh Terms:

KEYWORDS: src-Family Kinases

MESH TERMS: metabolism

Chemical & Substance for Abstract: SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines. Information

Substance Name: src-Family Kinases

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for SRC-family kinases are activated in non-small cell lung cancer and promote the survival of epidermal growth factor receptor-dependent cell lines.

AFFILIATION: Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.

Country: United States

AGENCY: United States NCI

GRANT: P50 CA70907

ACRONYM: CA

MEDLINETA: Am J Pathol

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