Regulation of IGF-2 gene expression in human chondrosarcoma derived cell lines : HCS-2/8 and -2/A

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In chondrocytes without vascula, autocrine function of insulin-like growth factor-2 (IGF-2) is very important for the growth and differentiation. Regulation on the expression of IGF-2 gene (IGF-2) in human chondrosarcoma derived cell lines (HCS-2/8 and -2/A) was investigated in order to explore the function of IGF-2.In human chondrocytes, all four promoters of IGF-2 are expressed, and consensus binding sequenses to the transcriptional factors ; EGR1 (early growth response gene product 1), SP-1 (specificity protein-1) and WT1 (Wilms tumor suppresor), are localizing over the transcriptional regulation region of IGF-2 promoters. Although the expression of SP-1 is very slight in both of normal chondrocytes and HCS-2/8, EGR1 expression in HCS-2/8 was higher than that in normal chondrocytes and WT1 expression in HCS-2/8 was lower thatn that in normal chondrocytes. This suggests that the abnormal growth of chondrosarcoma-derived HCS-2/8 may be induced with the synergistic effect between a positive function of EGR1 and negative one of WT1 to the growth enhancement during the initial growth phase.The effects of ascorbic acid in HCS-2/8 were positive to the gene expression of IGF-2, H19 (tumore suppresor), EGR1, SP-1, WT1, type-10 collagen alpha1, aggrecan and alkaline phosphatase, but negative to that of type-2 collagen alpha1. These results suggest that the role of ascorbic acid in chondrocytes may be as a growth and differetiational factor during the phases to differentiation from growth.The imprinting status of IGF-2 in HCS-2/8 was paternal alleles for all the promoters, and seem to be independent directly on the excess gene expression. On CDKNIC (p57^<KIP2>) in the imprinting cluster over human chromosome 11p15.5 region, a lacking of PA in the PAPA-repeat was detected for the paternal allele in HCS-2/8, and the expressed allele was maternal.