Strategy for developing transgenic assays for screening antineoplastic drugs that affect tubulin polymerization.
In this study we evaluated the antitumor efficacy of taxol in four solid tumor models derived from wap-ras line 69 transgenic mice. Taxol inhibited the growth of spontaneous salivary and mammary gland adenocarcinomas in wap-ras mice. In nude mice it was also effective against solid tumors caused by WR21 cells derived from a wap-ras salivary gland tumor. Taxol was not able to prevent tumor emergence in wap-ras/F mice, a subline of the wap-ras strain in which all males develop palpable mammary gland tumors between 1.5 and 3.0 months of age. Our data indicate the range of results that can be expected when this panel of related transgenic tumor models is used to study the antitumor effects of taxol and other therapeutic drugs that act by affecting tubulin polymerization. These models of ras-mediated neoplasia should prove useful for testing anticancer compounds with taxol-like mechanisms of action.
Porter
G M
GM
Department of Laboratory Animal Medicine & Surgery, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Armstrong
L
L
Nielsen
L L
LL
D000818:Animals; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D007150:Immunohistochemistry; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use*; D012468:Salivary Gland Neoplasms / Q000188:drug therapy; D014404:Tubulin / Q000187:drug effects
D014404:Tubulin; D017239:Paclitaxel