title: Reversible, p16-mediated cell cycle arrest as protection from chemotherapy.
abstract: A model system has been developed to explore the relationship between cell cycle arrest and chemotherapeutic toxicity. An isopropyl-1-thio-beta-D-galactopyranoside-inducible P16 construct was introduced stably into a melanoma cell line and used to promote G0-G1 arrest in the recipient cells. The state of arrest was reversible and did not compromise cell viability over a period of at least 7 days. Isopropyl-1-thio-beta-D-galactopyranoside-treated, arrested cells were significantly more resistant to the chemotherapeutic agents methotrexate (approximately 50 times), vinblastine (>100 times), and cisplatin (approximately 10 times) compared to controls. This strategy of protection from chemotherapy exploits one of the basic genotypic differences between normal cells and tumor cells: the integrity of genetic pathways that regulate growth.
authors.affiliation: Myriad Genetics, Inc., Salt Lake City, Utah 84108, USA.
authors.forename: S
authors.initials: S
authors.lastname: Stone
authors.forename: P
authors.initials: P
authors.lastname: Dayananth
authors.forename: A
authors.initials: A
authors.lastname: Kamb
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002352:Carrier Proteins / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004334:Drug Administration Schedule; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D000970:Antineoplastic Agents; D002352:Carrier Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D014747:Vinblastine; D002945:Cisplatin; D008727:Methotrexate