Stark Andreas M, Schem Christian, Maass Nicolai, Hugo H H, Jonat Walter, Mehdorn H Maximilian, Held-Feindt Janka
Department of Neurosurgery, University of Schleswig-Holstein Medical Center, Campus Kiel, Schittenhelmstrasse 10, 24105 Kiel, Germany.
Neurol Res. 2010 Apr;32(3):303-8. doi: 10.1179/016164109X12518779082192. Epub 2009 Nov 11.
The suppressor gene maspin (Serpin B5) is a promising candidate for future treatment. We have examined the messenger RNA (mRNA) and protein expression of maspin in normal breast tissue, breast cancer primaries, brain metastases and breast cancer cell lines. Results were compared to hormone receptor expression and proliferation index.
Maspin mRNA expression was examined by real-time polymerase chain reaction in fresh frozen human samples and breast cancer cell lines MCF-7, T47-D and MDA-MB-231. Maspin protein, estrogen and progesterone receptor expression as well as Ki-67 proliferation index were detected by immunohistochemistry from 16 patients with breast cancer primaries and breast cancer brain metastases.
In relation to normal breast tissue, maspin mRNA expression was decreased in primary tumors and again decreased in brain metastases. Normalized C(T) values were 1 (normal tissue), 0.3 (primary tumors) and 0.13 (brain metastases). Immunohistochemistry revealed same tendencies. In comparison to poorly invasive breast cancer cell lines, maspin mRNA expression was decreased in highly invasive and metastatic 231-parental cell lines. In contrast, maspin mRNA expression was increased in 231-brain, and it was not detectable in 231-bone. Patients with maspin-positive primary tumors showed longer survival.
This finding adds maspin to the list of metastasis suppressor genes possibly involved in the formation of breast cancer brain metastases.
抑癌基因组织蛋白酶抑制因子（丝氨酸蛋白酶抑制剂B5）是未来治疗很有前景的候选对象。我们检测了组织蛋白酶抑制因子在正常乳腺组织、原发性乳腺癌、脑转移瘤及乳腺癌细胞系中的信使核糖核酸（mRNA）和蛋白表达情况。并将结果与激素受体表达及增殖指数进行比较。
采用实时聚合酶链反应检测新鲜冷冻的人类样本及乳腺癌细胞系MCF-7、T47-D和MDA-MB-231中的组织蛋白酶抑制因子mRNA表达。通过免疫组织化学检测16例原发性乳腺癌和乳腺癌脑转移瘤患者的组织蛋白酶抑制因子蛋白、雌激素和孕激素受体表达以及Ki-67增殖指数。
与正常乳腺组织相比，原发性肿瘤中组织蛋白酶抑制因子mRNA表达降低，脑转移瘤中再次降低。标准化C(T)值分别为1（正常组织）、0.3（原发性肿瘤）和0.13（脑转移瘤）。免疫组织化学显示出相同趋势。与侵袭性较弱的乳腺癌细胞系相比，高侵袭性和转移性的231亲本细胞系中组织蛋白酶抑制因子mRNA表达降低。相反，231-脑转移细胞系中组织蛋白酶抑制因子mRNA表达增加，而在231-骨转移细胞系中未检测到。组织蛋白酶抑制因子阳性原发性肿瘤患者的生存期更长。
这一发现使组织蛋白酶抑制因子加入到可能参与乳腺癌脑转移形成的转移抑制基因名单中。
