Hasegawa Seiichi, Miyoshi Yasuo, Egawa Chiyomi, Ishitobi Makoto, Taguchi Tetsuya, Tamaki Yasuhiro, Monden Morito, Noguchi Shinzaburo
Department of Surgical Oncology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.
Clin Cancer Res. 2003 Aug 1;9(8):2992-7.
The relationship of intratumoral mRNA levels of class I and III beta-tubulin isotypes with clinical response to docetaxel has been studied in breast cancer patients.
Expression of class I and class III beta-tubulin mRNA levels was determined by a real-time PCR in breast cancer tissues obtained from 39 patients with locally advanced breast cancers (n = 26) or locally recurrent breast cancers (n = 13) before docetaxel treatment.
Class I beta-tubulin mRNA levels of responders [6.58 +/- 1.43 (x10(2)), mean +/- SE] were significantly (P = 0.002) lower than those of nonresponders [14.97 +/- 2.95 (x10(2))], and class III beta-tubulin mRNA levels of responders (1.38 +/- 0.40) were also significantly (P = 0.003) lower than those of nonresponders (7.43 +/- 2.77). Breast cancers were divided into four groups according to the expression status of class I and class III beta-tubulin isotype mRNA, i.e., the class I-high/class III-high group (n = 13), the class I-high/class III-low group (n = 7), the class I-low/class III-high group (n = 7), and the class I-low/class III-low group (n = 12). The class I-high/class III-high group showed a very low response rate (15%), whereas the class I-low/class III-low group showed a very high response rate (75%). The class I-high/class III-low group and the class I-low/class III-high group showed intermediate response rates of 57% and 43%, respectively.
These results demonstrate that high expression of class I and class III beta-tubulin isotype mRNA is significantly associated with docetaxel resistance, and determination of class I and class III beta-tubulin isotype mRNA levels would be useful in the prediction of response to docetaxel.
在乳腺癌患者中研究了I类和III类β-微管蛋白亚型的肿瘤内mRNA水平与多西他赛临床反应的关系。
通过实时PCR测定了39例局部晚期乳腺癌（n = 26）或局部复发性乳腺癌（n = 13）患者在多西他赛治疗前获取的乳腺癌组织中I类和III类β-微管蛋白mRNA水平的表达。
反应者的I类β-微管蛋白mRNA水平[6.58±1.43（×10²），平均值±标准误]显著低于无反应者[14.97±2.95（×10²）]（P = 0.002），反应者的III类β-微管蛋白mRNA水平（1.38±0.40）也显著低于无反应者（7.43±2.77）（P = 0.003）。根据I类和III类β-微管蛋白亚型mRNA的表达状态将乳腺癌分为四组，即I高/III高组（n = 13）、I高/III低组（n = 7）、I低/III高组（n = 7）和I低/III低组（n = 12）。I高/III高组显示出非常低的反应率（15%），而I低/III低组显示出非常高的反应率（75%）。I高/III低组和I低/III高组的反应率分别为中等水平，即57%和43%。
这些结果表明，I类和III类β-微管蛋白亚型mRNA的高表达与多西他赛耐药显著相关，测定I类和III类β-微管蛋白亚型mRNA水平有助于预测多西他赛的反应。
