Coexpression of Multiple Sertoli Cell and Leydig Cell Marker Genes in the Spontaneous Testicular Tumor of F344 Rat: Evidence for Phenotypical Bifurcation of the Interstitial Cell Tumor

The development of testicular tumor has been frequently observed in some laboratory rat strains. In the present study, we have further characterized the testicular tumor that spontaneously develops in the F344 rat (F344/Jcl). Tumor cells first appeared in the interstitium and developed into multifocal nodular lesions. In the later stage, the whole testes were occupied by tumor cells that consisted of three different types of cells in morphological appearance: large clear type, small eosinophilic type and intermediate type. To determine the character of these cells, we examined the expression of marker genes for Sertoli cells (e.g., transferrin) and Leydig cells (e.g., 3β–hydroxysteroid dehydrogenase 1 (3β–HSD 1)). Transferrin and 3β–HSD 1 mRNAs were found in all 8 tumor samples analyzed hy northern blotting. By in situ hybridization, we observed a substantial amount of 3β–HSD 1 mRNA and little or no transferrin mRNA in the large clear cells. In contrast, the small eosinophilic cells showed little or no 3β–HSD 1 mRNA and a large amount of transferrin mRNA, suggesting that the tumor was a mixture of at least two types of cells. Other Sertoli cell marker genes, such as cyclic protein 2 and sulfated glycoprotein 2, were expressed in all 8 tumors analyzed, and testin and steel factor (SLF), the c–kit receptor ligand, were also expressed in some of the tumors (testin, 75%; SLF, 25%), while other Leydig cell markers, LH receptor and c– kit , were expressed in 87% and 80% of the tumors, respectively. These results indicate that the spontaneous testicular tumor of F344 rat is of interstitium origin, showing phenotypical bifurcation possibly via transdifferentiation.