Identification of intracellular factors involved with apoptosis induction by TGF-β family

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Members of TGF-β superfamily are implicated in regulation of various life phenomenons, including initial development, organ formations and tumor formation. We found that activin A and BMP-2 inhibited cell growth of B cell hybridoma, HS-72 and examined its intracellular transduction mechanism. In the present study, we used three kinds of cells (HS-72 cells, LS-1 cells, and LS-12 cells) and investigated difference of sensitivity for activin A to these cells by flow cytometric analysis.We reported that activin A induced cytotoxic effects to HS-72, and induced G1 arrest in cell cycle and apoptosis at the concentration of 5-50 ng/ml. We clearly that retinoic acid induced a littel cytotoxity to HS-72 and G1 arrest in cell cycle, and that co-stimulation of retinoic acid and activin A potently induced G1 arrest and apoptosis. Activin A or retinoic acid have no effect to LS-1, however, co-stiluration of these factors induced G1 arrest and inclease of sub G1 rate of LS-1 cells. LS-12 showed intermediate type to Activin A and/or retinoic acid.Taken together, the results obtained in this study suggest that cross-talks between activin A and retinoic acid play an important role of the inductin of apoptosis in B lineage cells.