| Abstrakt: |
The mannose 6-phosphate/insulin-like growth fac tor-II receptor (M6P/IGF2R) functions in the in tracellular trafficking of lysosomal enzymes, the activation to the potent growth inhibitor, transform ing growth factor β, and the degradation of IGF2, a mitogen often overproduced in tumours. We have recently shown that 70% of human hepatocellular tumours have loss of heterozygosity (LOH) at the M6P/IGF2R locus which maps to chromosome 6q26-27. Using a coarse screen, we have now identified point mutations in the remaining allele of 25% of human hepatocellular carcinomas (HCCs) with LOH. These mutations give rise to truncated receptor protein and significant amino substitu tions, and provide evidence that the M6P/IGF2R gene functions as a tumour suppressor in human liver carcinogenesis. |
