INDUCIBLE EXPRESSION OF P21(WAF-1 CIP-1/SDI-1) FROM A PROMOTER CONVERSION RETROVIRAL VECTOR/

Constitutive, high-level expression of the potentially therapeutic WAF -1/CIP-1/SDI-1 gene is incompatible with cell growth. A promoter conve rsion retroviral vector carrying the WAF-1/CIP-1/SDI-1 gene under the transcriptional control of the glucocorticoid inducible promoter of mo use mammary tumor virus was used to infect human bladder carcinoma or feline kidney cells. Reduced cell growth due to a greater proportion o f cells being in the G(0)/G(1) phase of the cell cycle was observed wh en WAF-1/CIP-1/SDI-1 expression was activated by addition of glucocort icoid hormone. This system demonstrates the potential long-term therap eutic use of WAF-1/CIP-1/SDI-1 delivered by retroviral vectors for inh ibiting the growth of rapidly proliferating cells, Moreover. the condi tional expression of genes such as WAF-1/CIP-1/SDI-1 from such retrovi ral vectors may facilitate analysis of their function.