Maudelonde T, Domergue J, Henquel C, Freiss G, Brouillet J P, Simony J, Pujol H, Rochefort H
Unité INSERM 148 Hormones et Cancer, Montpellier, France.
Cancer. 1989 Apr 1;63(7):1265-70. doi: 10.1002/1097-0142(19890401)63:7<1265::aid-cncr2820630706>3.0.co;2-z.
The pro-cathepsin D of Mr 52,000 is regulated by estrogens via the estrogen receptor (RE) and is secreted by breast cancer cells in vitro. In an attempt to predict the hormone responsiveness of breast cancer in vivo, we have assayed total 52K cathepsin D and its precursor in the primary breast cancer cytosol of 36 patients treated before surgery with 30 mg of tamoxifen daily for 1 to 5 weeks (average, 3 weeks). Compared to a similar control population, total 52K cathepsin D was increased by tamoxifen (P = 0.02) but less so than its precursor (P less than 0.001). Furthermore, 45% of the RE-positive tumors from tamoxifen-treated patients had a higher cathepsin D precursor concentration than the same type of tumor from control patients, or than RE-negative tumors from tamoxifen-treated patients. This 3-week challenge test was probably too short to avoid partial estrogenic activity of tamoxifen (flare) and the authors infer that longer time of treatment would decrease rather than increase the concentration of cathepsin D in the RE-responsive tumors. However, two cancers from patients with relapses after prolonged tamoxifen treatment (greater than 6 months) also had high concentrations of 52K cathepsin D and its precursor. The authors conclude that the concentration of cathepsin D and its precursor in breast cancer cytosol can be increased by short-term tamoxifen treatment, suggesting that these tumors are estrogen responsive.
分子量为52,000的组织蛋白酶D原受雌激素通过雌激素受体（RE）调控，且在体外由乳腺癌细胞分泌。为了预测体内乳腺癌的激素反应性，我们检测了36例患者原发性乳腺癌细胞溶质中总的52K组织蛋白酶D及其前体，这些患者在手术前接受了每日30毫克他莫昔芬治疗1至5周（平均3周）。与相似的对照人群相比，他莫昔芬使总的52K组织蛋白酶D增加（P = 0.02），但其前体增加得更多（P小于0.001）。此外，他莫昔芬治疗患者中45%的RE阳性肿瘤，其组织蛋白酶D前体浓度高于对照患者的同类型肿瘤，或高于他莫昔芬治疗患者中的RE阴性肿瘤。这种为期3周的激发试验可能太短，无法避免他莫昔芬的部分雌激素活性（flare），作者推断更长时间的治疗会降低而非增加RE反应性肿瘤中组织蛋白酶D的浓度。然而，在长期他莫昔芬治疗（大于6个月）后复发的两名患者的癌症中，52K组织蛋白酶D及其前体浓度也很高。作者得出结论，短期他莫昔芬治疗可增加乳腺癌细胞溶质中组织蛋白酶D及其前体的浓度，提示这些肿瘤对雌激素有反应。
