Maeno Kazuma, Ito Ken-ichi, Hama Yoshihisa, Shingu Kiyoshi, Kimura Morihiko, Sano Muneaki, Nakagomi Hiroshi, Tsuchiya Shin-ichi, Fujimori Minoru
Department of Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
Cancer Lett. 2003 Jul 30;198(1):89-97. doi: 10.1016/s0304-3835(03)00279-9.
Mutation of the class I beta-tubulin gene has been reported to be one of the mechanisms that cause resistance to paclitaxel. To assess the relationship between paclitaxel-resistance and class I beta-tubulin gene mutation in breast cancer, Japanese patients with breast cancer were screened for the class I beta-tubulin gene mutation. Total RNA was isolated from 82 breast cancer specimens and the corresponding normal tissues. Twenty-four of the 82 patients were treated with paclitaxel preoperatively and 12 of them did not respond to the treatment. Of the 82 breast cancer patients, 15 (18.3%) had silent polymorphism in exon 4, Leu217Leu (CTG/CTA). However, no mutations showing amino acid substitution of the beta-tubulin gene were detected in any of the patients, including 12 patients who did not respond to paclitaxel. Class I beta-tubulin gene mutation with amino acid substitution was not detected in 82 breast cancer specimens. Our results suggest that mutation of the class I beta-tubulin gene is unlikely to play an important role in the mechanism of resistance to paclitaxel in breast cancer.
据报道,I类β-微管蛋白基因突变是导致对紫杉醇耐药的机制之一。为了评估乳腺癌中紫杉醇耐药性与I类β-微管蛋白基因突变之间的关系,对日本乳腺癌患者进行了I类β-微管蛋白基因突变筛查。从82份乳腺癌标本及相应的正常组织中分离出总RNA。82例患者中有24例术前接受了紫杉醇治疗,其中12例对治疗无反应。在82例乳腺癌患者中,15例(18.3%)在第4外显子存在沉默多态性Leu217Leu(CTG/CTA)。然而,在任何患者中均未检测到β-微管蛋白基因的氨基酸替代突变,包括12例对紫杉醇无反应的患者。在82份乳腺癌标本中未检测到具有氨基酸替代的I类β-微管蛋白基因突变。我们的结果表明,I类β-微管蛋白基因突变不太可能在乳腺癌对紫杉醇的耐药机制中起重要作用。