The proto-oncogene
recepteur d'origine nantais (RON, MST1R) and its alternatively spliced variants are involved in various
tumor biological processes, such as cell motility, adhesion, proliferation, apoptosis and epithelial-to-mesenchymal transition (EMT). RON overexpression and the occurrence of specific alternatively spliced RON
isoforms have been detected in
ovarian cancer. In the present study, we evaluated the role and regulation of
cancer-related RON splicing
isoforms in primary
ovarian cancer. Expression of RON variants (RONΔ165, RONΔ160) was determined in 45 primary
ovarian cancer and 4 physiological ovarian tissue specimens by RT-PCR and western blot analysis. The results were correlated to clinicopathological parameters. Additionally, expression of
splicing factors with known involvement in RON alternative splicing regulation was examined. Increased RON levels were detected in all
tumor samples (p=0.001) without differences between the primary
tumors and
metastases. Alternative RON variants were present in the majority of
tumor samples (39 of 45; 86.67%). Potential RONΔ165 occurred more often (82.22%) than potential RONΔ160 or RONΔ155 (24.40%). Several significant correlations of RON and
splicing factor expression [e.g. ASF/SFRS1 (p=0.035)] were detected. Correlations of RON expression to clinicopathological parameters were not observed. Significant
splicing factor interactions (e.g. SRp55/SRp75: p<0.001) were observed in
tumor samples with alternative RON splicing. Our data demonstrated upregulated RON
isoform expression and significant changes in
splicing factor expression in primary
ovarian cancer. These findings account for an essential regulatory interplay of
splicing factor-driven alterations in the RON alternative splicing pattern with subsequent
tumor biological consequences in
ovarian cancer.