Relationship between Sloan-Kettering virus expression and mammalian follicular development

Summary Sloan-Kettering virus gene, a product of a cellular proto-oncogene c-Ski is a unique nuclear pro-oncoprotein and belongs to the Ski/Sno proto-oncogene family. The aim of the present study was to locate Ski protein in rat ovaries in order to find insights into the possible involvement of Ski in follicular development. First, expression of c-Ski mRNA in the ovaries of adult female rats was confirmed by RT-PCR. Then, ovaries obtained on the day of estrus were subjected to immunohistochemical analysis for Ski and proliferating cell nuclear antigen (PCNA) in combination with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RT-PCR and in situ hybridization revealed that c-Ski mRNA was expressed in the ovaries of the adult rat on the day of estrous and localized mainly in the granulose cells. Ski was expressed in granulosa cells that were positive for TUNEL, but negative for PCNA, regardless of the shape and size of follicles. Expression of Ski in TUNEL-positive granulosa cells, but not in PCNA-positive granulosa cells, was also verified in rats having atretic follicles with double staining. These results indicate that Ski is profoundly expressed in the granulosa cells of atretic follicles, but not in growing follicles. Based on the present findings, Ski may play a role in the apoptosis of granulosa cells during follicular atresia.