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Expression of the Short Form of RON/STK in Feline Mammary Carcinoma
Lorella Maniscalco1, Silvia Guil-Luna2,3, Selina Iussich1
11 Department of Veterinary Sciences, University of Turin, Grugliasco, Italy.
Abstract:
RON is a tyrosine kinase receptor activated by the macrophage-stimulating protein (MSP) ligand that is overexpressed in human breast cancer. In humans, RON protein can be present in different isoforms, and the most studied isoform is represented by the short form of RON ( sf-RON), which is generated by an alternative promoter located in intron 10 of the RON complementary DNA (cDNA). It plays an important role in breast cancer progression. Considering the many similarities between feline mammary carcinoma (FMC) and human breast cancer, the aim of this study was to investigate the expression of both RON and MSP in FMCs and to identify the presence of the sf-RON transcript. Tissue samples of spontaneous mammary tumors were collected from 60 queens (10 benign lesions, 50 carcinomas). All of the samples were tested for RON and MSP expression by immunohistochemistry; moreover, RNA was extracted from paraffin-embedded tissue samples, and the cDNA was tested by reverse transcription-polymerase chain reaction (RT-PCR) to identify the presence of sf-RON. Immunohistochemistry detected the expression of RON and MSP in 34 of 50 (68%) and 29 of 50 (58%) FMCs, respectively. RT-PCR revealed the presence of the short-form in 18 of 47 (38%) FMCs. This form originates, as in humans, from an alternative promoter (P2), and it codes for the proper feline short form ( sf-RON). sf-RON expression was associated with poorly differentiated tumors and with a shorter disease-free ( P < .05; hazard ratio [HR], 2.2) period and a shorter survival ( P < .05; HR, 2.2). These results support FMC as a suitable model in comparative oncology and identify sf-RON expression as potential predictor of outcomes for this disease.
Insights
Researchers studied feline mammary carcinoma (FMC) and found the short form of RON (sf-RON) is expressed in tumors. sf-RON presence indicates a poorer prognosis, supporting FMC as a comparative oncology model.
Area of Science:
- Oncology
- Molecular Biology
- Veterinary Medicine
Background:
- The RON receptor tyrosine kinase and its ligand, macrophage-stimulating protein (MSP), are implicated in human breast cancer progression.
- The short form of RON (sf-RON) arises from an alternative promoter and plays a role in human breast cancer.
- Feline mammary carcinoma (FMC) shares similarities with human breast cancer, making it a valuable model for comparative studies.
Purpose of the Study:
- To investigate the expression of RON and MSP in feline mammary tumors.
- To identify the presence and origin of the sf-RON transcript in FMCs.
- To evaluate the association of sf-RON expression with tumor characteristics and patient outcomes.
Main Methods:
- Immunohistochemistry was used to detect RON and MSP expression in 50 FMCs and 10 benign lesions.
- RNA was extracted from paraffin-embedded tissues for RT-PCR analysis to identify sf-RON transcripts.
- Statistical analysis, including hazard ratios, was performed to assess the impact of sf-RON on disease-free period and survival.
Main Results:
- RON and MSP expression was detected in 68% and 58% of FMCs, respectively.
- The sf-RON transcript was identified in 38% of FMCs, originating from an alternative promoter (P2) as seen in humans.
- sf-RON expression correlated with poorly differentiated tumors, shorter disease-free periods (HR, 2.2), and reduced survival (HR, 2.2).
Conclusions:
- Feline mammary carcinoma serves as a relevant model for comparative oncology research.
- The expression of sf-RON in FMCs is linked to adverse prognostic factors.
- sf-RON may serve as a potential predictive biomarker for outcomes in feline mammary carcinoma.
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