bcl-x is a member of the bcl-2 family of genes and by alternative splicing gives rise to two distinct mRNAs: bcl-xL and bcl-xS. We have previously investigated the expression of Bcl-x in neuroblastoma (NB) cell lines and have shown that Bcl-xL is expressed and functions to inhibit chemotherapy-induced apoptosis. However, none of the NB cell lines expressed Bcl-xS. The aim of the present study was to determine the effects of Bcl-xS expression on the viability of NB cells. A panel of NB cell lines (CHP-382, GOTO, SHEP-1, SHSY-5Y, and GI-CA-N) were infected with either a bcl-xS adenovirus (pAdRSV-bcl-xS) or a control virus (pAdRSV-lac-z). NB cells showed loss of viability with both viruses, although the bcl-xS virus was most toxic. Importantly, infection with the bcl-xS adenovirus resulted in rapid loss of cell viability, DNA fragmentation, and morphological features of apoptosis even in NB cells transfected to overexpress Bcl-2 and Bcl-xL. These findings suggest that deregulated expression of Bcl-xS using an adenovirus may provide a novel mechanism for initiating cell death in tumors that express Bcl-2 or Bcl-xL.
This work was supported by National Institute of Child Health and Human Development Grant CHRC HD2880-3 (to V. P. C.) and NIH Grant RO1 CA70057 to (G. N). M. F. C. is supported by American Cancer Society Grant EDT-75339, NIH Grant CA67140. U.S. Army Medical Grant 941407, Charlotte Geyer Foundation Grant CA-67140, and Susan G. Komen Breast Cancer Foundation Grant 953382. M. G. D. is a University of Michigan Cancer Center Pardee Fellow. P. H. is supported by the Janette Ferrantino Pediatric Hematology Research Foundation. G. N. is the recipient of a Research Career Development Award from the NIH.