Bcl-2 expression in neuroblastoma is differentially regulated by differentiation inducers.

ABSTRACT

Neuroblastoma is characterized by differentiation in vivo and in vitro, and the process is known to be associated with changes in various gene expressions, among which is the bcl-2 gene whose major function may be potentially involved in the resistance to anticancer chemotherapy. We investigated the changing patterns of bcl-2 expression in neuroblastoma cell lines according to differentiation to assess whether the expression patterns can be differentially modulated by different types of differentiation inducers. Differentiation was induced in two neuroblastoma cell lines [SK-N-SH, SK-N-BE(2)] using all-trans-retinoic acid, gamma-interferon and EHS laminin, respectively. The levels of expression of bcl-2 were analysed before and after differentiation using immunoblotting and subsequent densitometry. The expression patterns of bcl-2 differed according to the type of differentiation inducers. Its expression increased when treated with retinoic acid and EHS laminin along with neuronal differentiation, while differentiation with gamma-interferon treatment was associated with decreased bcl-2 expression. Decreased expression of bcl-2 despite neuronal differentiation induced by gamma-interferon was thought to be important in that a certain differentiation pathway without increased drug resistance-related factor expression exists, which in turn has implications for the clinical application of gamma-interferon, combined with chemotherapy.