TY - JOUR
T1 - Altered expression of Mβ2, the class II β-tubulin isotype, in a murine J774.2 cell line with a high level of taxol resistance
AU - Haber, Michelle
AU - Burkhart, Catherine A.
AU - Regl, Donna Lee
AU - Madafiglio, Janice
AU - Norris, Murray D.
AU - Horwitz, Susan Band
PY - 1995/12/29
Y1 - 1995/12/29
N2 - A series of taxol- and taxotere-resistant J774.2 cell lines has been characterized with respect to altered expression of β-tubulin, the cellular target for these drugs. Vertebrates have six classes of β-tubulin isotypes, each displaying a distinct pattern of expression. Although the functional significance of multiple β-tubulins has not been fully defined, there is evidence that the individual isotypes contribute to differences in microtubule dynamics and drug binding. To determine if alterations in the expression of β-tubulin isotypes play a role in taxol resistance, a PCR- based methodology was developed that permits highly specific amplification of each of the six known murine β-tubulin isotypes. Two isotypes, Mβ5 and Mβ3, were expressed abundantly in the drug-sensitive parental J774.2 cells. Although expressed at an extremely low level in the parental cells, expression of the Mβ2 isotype was increased 21-fold (<0.005) in the cell line most resistant to taxol. These findings suggest that a cell can alter its relative tubulin isotype composition in response to an external stress and specifically imply that altered expression of Mβ2, the class II β- tubulin isotype, may contribute to the development of high resistance to taxol.
AB - A series of taxol- and taxotere-resistant J774.2 cell lines has been characterized with respect to altered expression of β-tubulin, the cellular target for these drugs. Vertebrates have six classes of β-tubulin isotypes, each displaying a distinct pattern of expression. Although the functional significance of multiple β-tubulins has not been fully defined, there is evidence that the individual isotypes contribute to differences in microtubule dynamics and drug binding. To determine if alterations in the expression of β-tubulin isotypes play a role in taxol resistance, a PCR- based methodology was developed that permits highly specific amplification of each of the six known murine β-tubulin isotypes. Two isotypes, Mβ5 and Mβ3, were expressed abundantly in the drug-sensitive parental J774.2 cells. Although expressed at an extremely low level in the parental cells, expression of the Mβ2 isotype was increased 21-fold (<0.005) in the cell line most resistant to taxol. These findings suggest that a cell can alter its relative tubulin isotype composition in response to an external stress and specifically imply that altered expression of Mβ2, the class II β- tubulin isotype, may contribute to the development of high resistance to taxol.
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U2 - 10.1074/jbc.270.52.31269
DO - 10.1074/jbc.270.52.31269
M3 - Article
C2 - 8537394
AN - SCOPUS:0029417352
SN - 0021-9258
VL - 270
SP - 31269
EP - 31275
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 52
ER -