EXPRESSION AND SUBCELLULAR-LOCALIZATION OF THE MYC SUPERFAMILY PROTEINS - C-MYC, MAX, MAD1 AND MXI1 IN THE EPIPHYSEAL PLATE CARTILAGE CHONDROCYTES OF GROWING RATS

The changes in the expressions of the protooncogene protein c-Myc, its dimerization partner Max and the competitive inhibitors Mad1 and Mxi1 during the terminal differentiation of chondrocytes in vivo were inve stigated by immunocytochemistry. The four immunoreactivity patterns in the epiphyseal plate cartilage of growing rats, as they appeared unde r the light microscope, showed differences in protein expression level and intracellular distribution, with the chondrocyte developmental st age. c-Myc immunoreactivity was intense and mainly in the nuclei of pr oliferative chondrocytes. It decreased in the nuclei of mature chondro cytes and appeared in the cytoplasm. c-Myc immunoreactivity increased in the fully-differentiated hypertrophic chondrocytes. Immunoreactivit y of the c-Myc dimerization partner Max was mainly in the nucleus of p roliferative chondrocytes and decreased as the chondrocytes matured. M ad1 immunoreactivity was also concentrated in the nucleus of prolifera tive chondrocytes, but was mainly in the cytoplasm of mature chondrocy tes and almost lost from the hypertrophic chondrocytes. Lastly, there was Mxi1 immunoreactivity in the nucleus and cytoplasm of proliferativ e, mature and early hypertrophic chondrocytes and the cytoplasm staini ng was more sustained than in the nucleus. There was little labeling i n late hypertrophic chondrocytes. The electron microscope pictures cor roborated these findings and showed the subcellular distributions of t he immunolabelings. The gold particles reflecting Mad1 frequently form ed patches and those for Mxi1 appeared to accumulate within the mitoch ondria of all chondrocytes. The variations in immune-patterns and intr acellular distributions suggest that each protooncogene protein has sp ecific roles in the functional changes in the chondrocytes at each ste p of their terminal differentiation.