DIFFERENTIAL EXPRESSION OF TIS21 AND TIS1 GENES IN THE VARIOUS ORGANSOF BALB C MICE, THYMIC CARCINOMA TISSUES AND HUMAN CANCER CELL-LINES/

As a part of a series of investigations on the functions of TIS21 and TIS1 genes, we measured in vivo 12-O-tetradecanoylphorbol-13-acetate ( TPA) inducibility of primary response genes (TIS21, TIS8 and TIS1) in the Balb/c mice and the changes of TIS gene expression in thymic carci noma tissues and A549 and NCIH69 human lung cancer cell lines. In vivo induction of the TIS genes (TIS21, -8 and -1) by intraperitoneal inje ction of TPA was dramatic only at the needle contact site, i.e. in the abdominal muscle: not in the thigh muscle. Expression of TIS21 and TI S1 in the Balb/c mice thymus, lung, stomach and spleen was very strong (Lim IK et al. 1994a), regardless of TPA injection. Thymic carcinoma tissues developed in SV40-T-antigen-containing transgenic mice did not express TIS21 and TIS1, and expressed TIS8 weakly. Interestingly, ind uction of TIS21 expression was obliterated in the human lung cancer ce lls; A549 cells completely lost the ability to express TIS21 after a c ombined treatment of TPA and cycloheximide. We also measured the induc tion of TIS genes by TPA and/or cycloheximide in Raw264.7 mouse macrop hage cells and U937 human histiocytic lymphoma cells. However, the ind uction profile was quite different; repressed and deregulated expressi on in the U937 cells as compared to rapid and transient induction of T IS genes in the Raw264.7 cells. These data may suggest a repressed exp ression of TIS21 and TIS1 in the cancer tissues and cells derived from the organs that constitutively express TIS21 in mice and in human can cer cells.