Inducible expression of p21WAF-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 conversion retroviral vector carrying the WAF-1/CIP-1/SDI-1 gene under the transcriptional control of the glucocorticoid inducible promoter of mouse mammary tumor virus was used to infect human bladder carcinoma or feline kidney cells. Reduced cell growth due to a greater proportion of cells being in the G0/G1 phase of the cell cycle was observed when WAF-1/CIP-1/SDI-1 expression was activated by addition of glucocorticoid hormone. This system demonstrates the potential long-term therapeutic use of WAF-1/CIP-1/SDI-1 delivered by retroviral vectors for inhibiting the growth of rapidly proliferating cells. Moreover, the conditional expression of genes such as WAF-1/CIP-1/SDI-1 from such retroviral vectors may facilitate analysis of their function.
Mrochen
S
S
Institute of Molecular Virology, GSF-National Research Center for Environment and Health, Universität München, Germany.
Klein
D
D
Nikol
S
S
Smith
J R
JR
Salmons
B
B
Günzburg
W H
WH
D000818:Animals; D002415:Cats; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics*; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D005822:Genetic Vectors / Q000138:chemical synthesis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009052:Leukemia Virus, Murine / Q000235:genetics*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D051379:Mice; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D003907:Dexamethasone