Vinorelbine induces beta3-tubulin gene expression through an AP-1 Site.
Although the correlation between beta3-tubulin expression level in tumors has been well correlated with clinical outcome in patients receiving microtubule-targeted agents, the regulation of this protein remains poorly understood. Recently, new insight of regulatory processes was offered with the cloning of the gene promoter. In this study beta3-tubulin gene expression was induced in response to exposure to various antimicrotubule agents such as vinorelbine and paclitaxel. The exploration of the beta3-tubulin gene promoter by successive deletions followed by site-directed mutagenesis led to the localization of a vinorelbine-responsive element containing an activator-protein 1 (AP-1) site. Among the various antimicrotubule agents tested, it appeared that the implicated AP-1 site was activated only after exposure to vinorelbine. This study confirms the inducible nature of the beta3-tubulin gene promoter.
Saussede-Aim
Jennifer
J
Laboratoire de Cytologie Analytique, Faculté de Medecine Rockefeller, 8 Avenue Rockefeller, 69008 Lyon, France. jennifer.saussede-aim@laposte.net
Matera
Eva-Laure
EL
Herveau
Stephanie
S
Rouault
Jean-Pierre
JP
Ferlini
Christiano
C
Dumontet
Charles
C
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D050436:Regulatory Elements, Transcriptional; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014404:Tubulin / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077235:Vinorelbine
D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D011838:Radiation-Sensitizing Agents; C498585:TUBB3 protein, human; D018808:Transcription Factor AP-1; D014404:Tubulin; D014747:Vinblastine; D008156:Luciferases; D000077235:Vinorelbine