Novel human alpha-fetoprotein mRNA isoform lacking exon 1 identified in ovarian yolk sac tumor.

OBJECTIVE: Alpha-fetoprotein (AFP) is a major fetal serum protein, the biologic role of which has not been not fully elucidated. Recently, existence of a novel AFP mRNA isoform (del.1 AFP mRNA isoform), which is transcribed from the intron A (the intron between exons 1 and 2), has been reported in murine yolk sac and fetal liver. In the present study, we intended to identify the human homologue of the murine AFP mRNA isoform in the yolk sac tumor. METHODS: To investigate the existence of the mRNA isoform (which we termed the AFP-C mRNA isoform), reverse transcription-polymerase chain reaction (RT-PCR) was used. Moreover, the expression analysis of the AFP-C cDNA isoform using the AFP-negative human cell line was carried out. RESULTS: RT-PCR revealed the existence of the AFP-C mRNA isoform in the yolk sac tumor and human hepatocellular carcinoma cells. The expression analysis darified that the molecular size of the AFP-C was approximately 65 kd, and that the protein was not secreted, in contrast to the traditional AFP. CONCLUSION: From these results, the existence of the AFP-C mRNA isoform has been demonstrated for the first time in humans. The AFP-C located in cytoplasm possibly plays physiologic/pathogenic roles distinct from those of the traditional AFP in the yolk sac tumor and hepatocellular carcinoma.