CHARACTERIZATION OF THE ICF SYSTEM AND ANALYSIS OF THE POSSIBLE MOLECULAR MECHANISMS LEADING TO IGF-II OVEREXPRESSION IN A MESOTHELIOMA

The expression of members of the IGF system in a mesothelioma from a p atient suffering from hypoglycemia, in term placenta and HT29 colon ad enocarcinoma cells were compared. Very high levels of IGF-II mRNA and protein were detected in the mesothelioma. Moreover, half of the IGF-I I protein took the high-molecular-weight form. We also analyzed the pa rental imprinting status and the promoter usage of the IGF-II gene. Ou r results showed loss of imprinting (LOI) in the mesothelioma while th e imprinting was maintained in HT29 cells, expressing moderate levels of the transcript. Promoter P4 was active in the three tissues we anal yzed, whereas IGF-II mRNA transcription from promoter P3 was only dete cted in the mesothelioma and the placenta, expressing comparably high levels of the transcript. IGF-II gene structure was identical in the a nalyzed tissues and cells. The type-I receptor mRNA expression was ver y low in the tumor. IGFBP-2, -4 and -5 mRNAs were detected in the meso thelioma, while IGFBP-2, -3 and -5 transcripts were detected in the pl acenta. IGFBP-1 and -6 transcripts were not detected.