Microtubule Associated Protein (MAP)-Tau: a novel mediator of paclitaxel sensitivity in vitro and in vivo.
Microtubule binding protein Tau was recently identified through gene expression analysis of human breast cancer tissues as a novel marker of response to paclitaxel. This article reviews these recent findings and provides additional information to support the role of Tau as an emerging marker and mediator of paclitaxel sensitivity. Low expression of Tau is associated with increased sensitivity to paclitaxel in human breast cancer as well as in a broad range of cell lines. Down regulation of Tau in cell lines by siRNA increases their sensitivity to paclitaxel but not to anthracycline chemotherapy. We propose that this is due to increased paclitaxel binding to microtubules when microtubules are assembled in the presence of low concentrations (or absence) of Tau compared to microtubules that are formed in the presence of physiological (or higher) levels of Tau.
Wagner
P
P
Deparment of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77230-1439, USA.
Wang
B
B
Clark
E
E
Lee
H
H
Rouzier
R
R
Pusztai
L
L
D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014404:Tubulin / Q000737:chemistry; D016875:tau Proteins / Q000378:metabolism*
D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014404:Tubulin; D016875:tau Proteins; D017239:Paclitaxel