Expression of growth factor receptors, the focal adhesion kinase, and other tyrosine kinases in human soft tissue tumors

Timothy M. Weiner, Edison T. Liu, Rolf J. Craven, William G. Cance

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Background: The tyrosine kinases are a family of genes that includes many growth factor receptors and protooncogenes. They appear to have a role in many cancers, but have not been systematically studied in the pathogenesis and progression of human sarcomas. Methods: To characterize the protein tyrosine kinases that are expressed in human sarcomas, we used a polymerase chain reaction (PCR)-based method to construct kinase-specific cDNA libraries from low-grade and high-grade primary tumors. Thereafter, individual tyrosine kinase gene expression was assessed in a panel of sarcoma cell lines and primary tumors using Northern blotting and PCR. Results: We identified 19 species of tyrosine kinase genes, including many growth factor receptors, the human homolog of the focal adhesion kinase (FAK) gene, and a novel trk-related kinase designated HGK2. Messenger RNA expression analyses showed relative overexpression of the two forms of the platelet-derived growth factor receptors (PDGFRs) with expression of the α form restricted to a subgroup of high-grade and metastatic sarcomas. We were unable to demonstrate coexpression of the PDGF isoforms in primary tumors that overexpressed the receptors, suggesting that a PDGF/PDGFR autocrine pathway may not be a central mechanism in the malignant transformation of sarcomas in vivo. FAK expression was observed in a variety of sarcomas, with increased levels in several high-grade and metastatic leiomyosarcomas. Conclusions: When grouped together by histologic cell type and grade, the expression data of the 19 kinases in primary tumors described a greater degree of heterogeneity than is generally appreciated by clinicopathologic classification schemes. This diversity suggests that sarcomas, even those that appear to be clinically similar, arise through a variety of molecular pathways involving tyrosine kinases.

Original languageEnglish
Pages (from-to)18-27
Number of pages10
JournalAnnals of Surgical Oncology
Volume1
Issue number1
DOIs
StatePublished - Jan 1994

Keywords

  • Focal adhesion kinase
  • Human sarcoma
  • Tyrosine kinase

ASJC Scopus subject areas

  • Surgery
  • Oncology

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