[59]

EFFECT OF SPACEFLIGHT ON EXPRESSION OF GENES REGULATING CELL GROWTH, CELL CYCLE, SIGNAL TRANSDUCTION, AND TUMOR SUPPRESSION IN T LYMPHOCYTES.  M.L. Lewis¹, L.A. Cubano², and M. Hughes-Fulford³. ¹Department of Biological Sciences, University of Alabama, Huntsville, ²Dept of Nephrology, Tulane University, ³Laboratory for Cell Research, VAMC, San Francisco, CA.

   We demonstrated on STS-76, 80 and 95 that leukemic T lymphocytes (Jurkat) do not grow in microgravity.  Conversely, ground controls doubled and after an initial loss of 30%, cells subjected to simulated shuttle launch vibration doubled between 24 and 48 hours.  Thus growth arrest in microgravity is not a direct result of shuttle launch vibration.  We also reported (Lewis and Cubano, Gravitational and Space Biology Bulletin, 2001 and Lewis et al., The FASEB Jour., 2001) that microgravity per se or other orbit-related factors alter cytoskeletal gene expression.  We now describe spaceflight effects on expression of genes that regulate growth, cell cycle, signal transduction and tumor suppression.  Gene expression in Jurkat cells flown on STS-95 and ground controls was evaluated by cDNA microarray at 24 and 48 hours (4,324 and >20,000 genes respectively).  We found marked differences in gene expression for tuberin, a tumor suppressor effecting arrest at G1/S; Cyclin-dependent kinase 6 (critical for G1/S progression); Prohibitin, an inhibitor of G1/S cycle traverse; an apoptosis-associated cleavage stimulating factor involved in cycle arrest at G0/G1; Endoglin, a cell surface antigen in the TGF-beta family; a TGF-beta superfamily protein that induces cytoskeletal reorganization and signaling via receptor complexes associated with serine and threonine kinases; and genes involved in dephosphorylation of inositol diphospate (IP₂).  Other signal transduction and transcription factor genes were also expressed differently in flown cells compared to ground.  In conclusion, these data provide information, at the gene expression level, that is critical to the understanding of growth arrest in spaceflown lymphocytes.

(Supported in part by NASA: NAG2-985 and NAGW-2-1286)

[