K-FGF PROTONCOGENE EXPRESSION IS ASSOCIATED WITH MURINE TESTICULAR TERATOGENESIS, BUT IS NOT INVOLVED DURING MOUSE TESTICULAR DEVELOPMENT

The k-FGF gene, which belongs to the family of the fibroblast growth f actor genes, is implicated in tumoral and developmental processes. It is expressed in embryonal carcinoma cells, in embryonic stem cells, du ring limb and tooth formation and in some germ cell tumors. However, t he expression of this protooncogene during testicular development as w ell its relationship to spontaneous teratogenesis have not been determ ined. Here we investigate L-FGF expression during testicular developme nt in mice, as well as in a spontaneous testicular teratoma (STT) and in the OTT6050 teratocarcinoma (TC) by Northern blotting, RT-PCR and i n situ hybridization. Several data indicate that k-FGF gene contains d ownstream regulatory sequences which bind octamer factors. One of thes e transcription factors which binds to k-FGF enhancer is Oct-4. Althou gh the k-FGF gene is activated by Oct-4 in embryonal carcinoma and emb ryonic stem cells and Oct-4 is expressed in the germ cells of the embr yo, our results indicate that there is no detectable k-FGF expression in mouse testicular germ cells at any stage of development. This indic ates that Oct-4 does not activate transcription of the L-FGF gene in m ouse germ cells, and that k-FGF is not implicated during testicular de velopment. We also show that there is a high L-FGF expression in the e xperimental OTT6050 TC, but only very low levels in a murine different iated STT, suggesting that k-FGF activation may be responsible for the genesis and development of STT, behaving as a marker of malignancy in these neoplasms.