The Ron proto-oncogene product is a phenotypic marker of renal oncocytoma.
The proto-oncogene product Ron is the receptor for macrophage stimulating protein, a scatter factor that stimulates cell proliferation, prevents apoptosis, and induces an invasive cell phenotype. We investigated the expression of Ron, Ki-67 (proliferation index), p53, and bcl-2 (proapoptotic and antiapoptotic proteins, respectively) in 50 renal tumors (19 clear cell carcinomas, 18 oncocytomas, 7 papillary cell carcinomas, 5 chromophobe cell carcinomas, and 1 carcinoma with sarcomatoid areas). In addition, we studied Ron in normal kidney and in the renal carcinoma cell line Caki-1. Immunostaining and Western blot showed Ron in normal kidney and in all oncocytomas but never in renal cell carcinomas or in Caki-1. In addition, Western blot showed that Ron was expressed in phosphorylated, i.e., active, form. Bcl-2 was strongly expressed in oncocytomas, whereas Ki-67 and p53 were much less expressed in oncocytomas than in carcinomas. These results indicate in Ron a marker that differentiates oncocytoma from the other renal epithelial tumors. We therefore think that Ron may prove to be a new tool for a sound and precise diagnosis of oncocytoma, a benign tumor that cannot always be distinguished from carcinomas at histologic examination. The overexpression of bcl-2, but not p53 in oncocytoma, suggests that the MSP/Ron system sustains the growth of oncocytoma by opposing apoptosis.
Rampino
Teresa
T
Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo University, Milano, Italy. t.rampino@smatteo.pv.it
Gregorini
Marilena
M
Soccio
Grazia
G
Maggio
Milena
M
Rosso
Renato
R
Malvezzi
Paolo
P
Collesi
Chiara
C
Dal Canton
Antonio
A
D018249:Adenoma, Oxyphilic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017209:Apoptosis; D014408:Biomarkers, Tumor; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D011498:Protein Precursors / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; C000715470:MAS1 protein, human; D011498:Protein Precursors; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C082332:macrophage stimulating protein; D017228:Hepatocyte Growth Factor