MOLECULAR-CLONING OF TA16, A TRANSCRIPTIONAL REPRESSOR THAT MAY MEDIATE GLUCOCORTICOID-INDUCED GROWTH ARREST OF LEIOMYOSARCOMA CELLS

The DDT, MF2 smooth muscle tumor cell line was derived from an estroge n/androgen-induced leiomyosarcoma that arose in the ductus deferens of a Syrian hamster, The growth of this cell line is arrested at the G0/ G1 phase of the cell cycle after treatment with glucocorticoids, To id entify the putative gene(s) that are potentially involved in this horm one-induced cell growth arrest, we have used a differential screening technique to clone those genes whose expression is induced or up-regul ated by glucocorticoids, A number of glucocorticoid response genes wer e thereby isolated from the leiomyosarcoma cells, One of these clones, termed TA16, was found to be markedly up-regulated by glucocorticoids in DDT, MF2 cells, but only marginally changed in GR1 cells, a glucoc orticoid-resistant variant that was selected from the wild type DDT, M F2 cell, Isolation and sequencing of its intact cDNA indicated that th e TA16 encodes a protein 485 amino acids long, and its sequence is clo sely homologous to a novel transcriptional repressor that presumably r epresses the transcription activity of some zinc finger transcriptiona l factors through a direct interaction, Transfection assays demonstrat ed that introduction of an antisense TA16 cDNA expression vector, cont rolled by an MMTV promoter, into the DDT, MF2 cell significantly relie ved the glucocorticoid-induced cell growth arrest, This finding sugges ts that TA16 might participate in the mediation of glucocorticoid-indu ced cell cycle arrest in leiomyosarcoma cells.