Tissue microarray analysis of hepatocyte growth factor/Met pathway components reveals a role for Met, matriptase, and hepatocyte growth factor activator inhibitor 1 in the progression of node-negative breast cancer.

Abstract

Numerous studies have demonstrated that overexpression of Met, the hepatocyte growth factor(HGF) receptor, plays an important role in tumorigenesis. Met activation can either occur through ligand-independent or -dependent mechanisms, both of which are mediated by a series of proteases and modulators. We studied the protein expression of several components of the HGF/Met pathway on a cohort of 330 node-negative breast carcinomas using a tissue microarray annotated with 30-year, disease-specific patient follow-up data. We examined HGF, matriptase (an activator of HGF expressed on mammary epithelial cell surfaces), HAI-I (the cognate inhibitor of matriptase), and the Met receptor itself. Our studies demonstrate tight correlation between the expression of HGF, matriptase, and Met in breast carcinoma. High-level expression of Met, matriptase, and HAI-I were associated with poor patient outcome. Met and HAI-I showed independent prognostic value when compared with traditional breast markers in a multivariate analysis. Intriguingly, antibodies against the intracellular but not the extracellular domain of Met were prognostic, suggesting that overexpression of the cytoplasmic-tail of Met, perhaps through cleavage or truncating mutation, may play an important role in breast cancer progression.

• Authors: Jung Y Kang, Marisa Dolled-Filhart, Idris Tolgay Ocal, Baljit Singh, Chen-Yong Lin, Robert B Dickson, David L Rimm, Robert L Camp
• Journal: Cancer research (Cancer Res) Vol. 63 Issue 5 Pg. 1101-5 (Mar 01 2003) ISSN: 0008-5472 [Print] United States
• PMID: 12615728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Membrane Glycoproteins
• Proteinase Inhibitory Proteins, Secretory
• Proto-Oncogene Proteins
• Receptors, Growth Factor
• SPINT1 protein, human
• Trans-Activators
• Hepatocyte Growth Factor
• MET protein, human
• Proto-Oncogene Proteins c-met
• Serine Endopeptidases
• matriptase
• ST14 protein, human
• Trypsin

Topics

• Breast Neoplasms (metabolism, pathology)
• Hepatocyte Growth Factor (biosynthesis, metabolism)
• Humans
• Membrane Glycoproteins (biosynthesis)
• Prognosis
• Proteinase Inhibitory Proteins, Secretory
• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-met
• Receptors, Growth Factor
• Serine Endopeptidases (biosynthesis)
• Trans-Activators (biosynthesis)
• Trypsin (biosynthesis)