Overexpression of the RON gene in human breast carcinoma

Piera Maggiora, Serena Marchio', Maria Cristina Stella, Maurizia Giai, Antonino Belfiore, Michele De Bortoli, Maria Flavia Di Renzo, Angela Costantino, Piero Sismondi, Paolo M. Comoglio

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Abstract

Constitutive activation of the RON gene, known to code for the tyrosine-kinase receptor for Macrophage Stimulating Protein (also known as Scatter Factor 2), has been shown to induce invasive-metastatic phenotype in vitro. As yet, nothing is known about the expression of this novel member of the MET-oncogene family in spontaneously occurring human cancers. Here we report that Ron is expressed at abnormally high levels in about 50% primary breast carcinomas (35/74 patients). Among these, the expression is increased more than 20-fold in 12 cases and the overexpressed protein is constitutively phosphorylated on tyrosine residues. Notably, Ron is only barely detectable in epithelial cells of the mammary gland, and its expression remains unchanged in benign breast lesions (including adenomas and papillomas). Overexpression was observed in different histotypic variants of carcinomas; it is associated with the disease at any stage and correlates with the post-menopausal status. In breast carcinoma cells grown in vitro activation of the Ron receptor resulted in proliferation, migration and invasion through reconstituted basement membranes. Altogether, these data suggest a role for the RON gene in progression of human breast carcinomas to the invasive-metastatic phenotype.

Original languageEnglish
Pages (from-to)2927-2933
Number of pages7
JournalOncogene
Volume16
Issue number22
Publication statusPublished - Jun 4 1998

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Keywords

  • Breast neoblasts
  • Protein-tyrosine kinase
  • RON

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Maggiora, P., Marchio', S., Stella, M. C., Giai, M., Belfiore, A., De Bortoli, M., Di Renzo, M. F., Costantino, A., Sismondi, P., & Comoglio, P. M. (1998). Overexpression of the RON gene in human breast carcinoma. Oncogene, 16(22), 2927-2933.