EXPRESSION OF RETINOBLASTOMA GENE IN HUMAN INTRACRANIAL NEOPLASMS

The retinoblastoma gene (RB) is a tumour suppressor gene, of which mutations are associated with carcinogenesis in a broad spectrum of human malignacies. To evaluate its putative role in tumorigenesis in intracranial tumours, we investigated cell lines derived from human gliomas and 91 fresh surgical specimens derived from a broad spectrum of intracranial tumours. We found 7 out of 24 cell lines with markedly reduced levels of the retinoblastoma gene protein (pRB) by Western blot and its mRNA by Northern blot analysis. Such a decrease of RB expression appeared not to be clonal, as none of these lines showed subpopulations with nuclear staining in immunocytochemistry. Loss or decreased expression of pRB, however, could only be detected in a small proportion of the glioma tissues. None of the informative lines or the 21 glioma specimens presented any mutation by Southern blot. Furthermore only in 2 out of 28 pituitary adenomas pRB was undetectable, which is interesting, as heterozygous RB-knockout mice are known to develop pituitary tumours. We conclude that alterations of the RB gene seem to be relevant in only a small subset of gliomas. Our findings also suggest, that not only loss, but also ineffectively low levels of pRB, which are not necessarily caused by mutations might play a role in the pathophysiology of tumours.