Retinoid-Induced Growth Arrest of Breast Carcinoma Cells Involves Co-Activation of Multiple Growth-Inhibitory Genes

Retinoids are used in leukemia therapy and chemoprevention of cancers. Treatment of MCF-7 breast carcinoma cells with low doses of retinoids induces gradual proliferation arrest with phenotypic markers of senescence. cDNA microarray hybridization and reverse transcription-polymerase chain reaction analysis showed that retinoid-induced growth arrest in MCF-7 cells is associated with strong induction of 13 genes. Four of these genes (IGF-binding protein 3, EPLIN, βIG-H3 and FAT10) have antiproliferative activity; EPLIN and βIG-H3 are also known to be selectively inhibited in transformed relative to normal cells. The functions of the induced genes may also account for other cellular effects of retinoids, including the proteasome-mediated protein degradation, increased cell adhesion, and retinoic acid synthesis. Only one of 13 strongly induced genes (ring finger protein TRIM31) contains a putative retinoid response element in its promoter; TRIM31 also shows the most rapid kinetics of induction by retinoids. I...