BCL-X(S) ENHANCES ADENOVIRAL VECTOR-INDUCED APOPTOSIS IN NEUROBLASTOMA-CELLS

bcl-x is a member of the bcl-2 family of genes and by alternative spli cing gives rise to two distinct mRNAs: bcl-x(L) and bcl-x(S). We have previously investigated the expression of Bcl-x in neuroblastoma (NB) cell lines and have shown that Bcl-x(L) is expressed and functions to inhibit chemotherapy-induced apoptosis. However, none of the NE cell L ines expressed Bcl-x(S). The aim of the present study was to determine the effects of Bcl-s(X), expression on the viability of NE cells. A p anel of NE cell lines (CHP-382, GOTO, SHEP-1, SHSY-5Y, and GI-CA-N) we re infected with either a bcl-x(S) adenovirus (pAdRSV-bcl-x(S)) or a c ontrol virus (pAdRSV-lac-z). NE cells showed loss of viability with bo th viruses, although the bcl-x, virus was most toxic. Importantly, inf ection with the bcl-x(S) adenovirus resulted in rapid loss of cell via bility, DNA fragmentation, and morphological features of apoptosis eve n in KB cells transfected to overexpress Bcl-2 and Bcl-x(L), These fin dings suggest that deregulated expression of Bcl-x(S) using an adenovi rus may provide a novel mechanism for initiating cell death in tumors that express Bcl-2 or Bcl-x(L).