Origin Neuroblastoma and Other Human Tumor Cell Lines of Neural Protooncogene in Bcl2 Differential Expression of Updated Version Citing Articles E-mail Alerts Differential Expression of Bcl2 Protooncogene in Neuroblastoma and Other Human Tumor Cell Lines of Neural Origin1

The bell protooncogene was originally discovered because of its in volvement in t(14;18) chromosomal translocations frequently found in non-Hodgkin's lymphomas. The expression of this gene is reported to be highly tissue specific, with bell mRNAs being readily detectable only in hematolymphoid tissues and brain. To explore the possible involvement of beli in neural tumors, we surveyed a variety of tumor cell lines for the presence of the p26-BCL2 protein by immunoprecipitation and ininiu-noblotting methods. Very high levels of BCL2 protein were found in three of nine neuroblastoma (NB) cell lines examined; these levels of p26-BCL2 were comparable to lymphoma cell lines that contain a t(14;18). Despite the impressive relative amounts of BCL2 protein, however, no structural alterations or changes in the methylation status of bell genes were detected in these NB cell lines by conventional Southern blotting. Of the other NB cell lines surveyed, three contained intermediate levels of BCL2 and another three cell lines had little or no detectable BCL2 protein, raising the possibility that determination of relative levels of BCL2 protein may help to segregate neuroblastomas into groups with different biological and clinical characteristics. BCL2 protein levels were not influenced by induction of neuronal differentiation with nerve growth factor in two of the two cell lines examined [SH-SY5Y (high BCL2); GICAN (low BO,2)| and did not correlate with N-MVf gene amplifi cation or expression of nerve growth factor receptors. NB cell lines that contained little or no detectable BCL2 protein, however, tended to contain significant proportions of flat epithelioid cells, whereas Ac/2-expressing cell lines were composed primarily of neuronal-like cells, suggesting that expression of this protooncogene correlates with the differentiation char acteristics of these tumor cell lines. In addition to NBs, lower levels of BCL2 protein were also found in a variety of other neural crest-derived tumors and tumor cell lines, including some neuroepitheliomas, Ewing's sarcomas, neurofibromas, and melanomas. With regard to tumors of central nervous system origin, bcl2 expression was absent from most medulloblastomas but was detected at moderate to low levels in a reti-noblastoma and some glioblastoma multiforme cell lines. Taken together, these findings imply that bell protooncogene expression is differentially regulated within the various lineages of cells that give rise to the nervous system.