COMPARATIVE MESSENGER-RIBONUCLEIC-ACID ANALYSIS OF IMMEDIATE-EARLY GENES AND SEX STEROID-RECEPTORS IN HUMAN LEIOMYOMA AND HEALTHY MYOMETRIUM

To shed light on the molecular mechanisms involved in the pathogenesis of uterine leiomyomas, transcript levels of the immediate early genes c-fos, c-myc, and c-jun and of the estrogen receptor (ER) and progest erone receptor (PR) were determined in tissue samples of human myometr ium and leiomyoma. The messenger RNA (mRNA) content was analyzed by RT -PCR. mRNAs for c-fos, c-myc, c-jun, ER, and PR were detected in all 1 8 samples of leiomyoma and corresponding myometrial tissue collected i n this study. Interestingly, in contrast to healthy tissues, we found a distinct and significant reduction of c-fos mRNA in the tumor. These data were substantiated by the finding of lowered c-Fos protein level s in leiomyomas tissues. Moreover, transcripts of c-jun and c-myc were less abundant in most of the leiomyomas than in the myometrium. This different expression of the protooncogenes in leiomyomas and myometriu m was independent of the phase of the menstrual cycle in which samples were collected. In contrast to the reduced transcript levels observed for the immediate early genes, the ER and PR mRNA contents of the lei omyomas and myometrium did not differ, These results were confirmed by immunohistochemical studies for ER and PR protein. In conclusion, our data show that the deregulated expression of protooncogenes, especial ly of c-fos, is Linked to the pathogenesis of leiomyomas. Confirmation of a potential role of downregulated c-fos levels for the benign char acter of these tumors requires further investigation. Additionally, th e findings suggest that sex steroids do not influence the different ex pression patterns of c-fos, c-myc, and c-jun in leiomyomas, as compare d with myometrium.