TABLE I Thiazolidinedione-regulated Genes That Control Cell Proliferation and Apoptosis Identified Using Gene Arrays

Function Gene Troglitazone

Rosiglitazone

M04 P04 M24 P24 M04 P04 M24 P24

Apoptosis Retinoic acid receptor alpha ++ ++ ++ ++ + + 0 -
Apoptosis Gadd45 ++ ++ ++ ++ + + 0 0
Cell cycle arrest Protein kinase A inhibitor ++ + - + ++ 0 ++ 0
Antiapoptosis Gas6 0 - - -- - - -- -
Apoptosis Transforming growth factor beta-inducible early protein ++ ++ 0 + 0 + 0 +
Tumor suppressor DEC1 ++ ++ + + 0 0 0 -
Apoptosis AD7c-neuronal thread protein + - + - ++ ++ ++ 0
Transcriptional repressor Activating transcription factor-3 ++ ++ ++ ++ + + 0 +
Transcriptional repressor Zinc nuclear finger 10 ++ + ++ + + + - -

[Genes were identified by cluster analysis or cutoff techniques described in the text for Mia Paca-1 (M) and Panc-1 (P) cells treated with TRO, ROSI, or vehicle control for 4 (04) or 24 hours (24). A program linked to PubMed/Gene Ontology was used to identify genes in this subset that regulate apoptosis and cell proliferation. Visualization of shades of gray from the heatmaps of Figures 4–6 correlates with expression levels of these identified genes. ++ = highly expressed (+ = increased expression), compared to matched untreated control, and correlates with white on heat map. 0 = no difference from control. - = a decrease in gene expression of treated group, compared to its matched control value. M = Mia Paca-1 cells; P = Panc-1 cells; 04 = 4 hours of treatment; 24 = 24 hours of treatment.]