Maass Nicolai, Nagasaki Koichi, Ziebart Martin, Mundhenke Christoph, Jonat Walter
Department of Obstetrics and Gynecology, Department of Gynecologic Oncology, University of Kiel, Michaelisstrasse 16, 24105 Kiel, Germany.
Clin Breast Cancer. 2002 Oct;3(4):281-7. doi: 10.3816/CBC.2002.n.032.
Maspin (mammary serpin) is an inhibitor of serine proteases with tumor suppressor activity in breast cancer. Maspin was originally identified by subtractive hybridization in normal breast epithelial cells, but its expression decreased during tumor progression. The loss of maspin gene expression with increasing malignancy is by transcriptional regulation. Maspin is known to be involved in invasion and metastasis, interact with the p53 tumor suppressor pathway, and act as an inhibitor of angiogenesis. The immunohistochemical analysis and reverse-transcription polymerase chain reaction of maspin in normal human breast tissue and breast carcinoma indicated a stepwise reduction of maspin expression during the progression from ductal carcinoma in situ to invasive carcinoma to lymph node metastasis. The lack of maspin expression in breast cancer seems to be associated with a short disease-free survival and supports maspin's function as an indicator for tumor aggressiveness and metastatic potential. New studies on the gene regulation of maspin provide evidence for promising potential of possible re-expression of maspin in tumor cells. The function of maspin as a tumor suppressor gene involved in tumor invasion, metastasis, and angiogenesis may not be limited to breast cancer.
组织蛋白酶抑制因子（乳腺丝氨酸蛋白酶抑制剂）是一种丝氨酸蛋白酶抑制剂，在乳腺癌中具有肿瘤抑制活性。组织蛋白酶抑制因子最初是通过正常乳腺上皮细胞的消减杂交法鉴定出来的，但在肿瘤进展过程中其表达会降低。随着恶性程度增加，组织蛋白酶抑制因子基因表达的丧失是通过转录调控实现的。已知组织蛋白酶抑制因子参与侵袭和转移，与p53肿瘤抑制途径相互作用，并作为血管生成的抑制剂发挥作用。对正常人类乳腺组织和乳腺癌中组织蛋白酶抑制因子的免疫组织化学分析及逆转录聚合酶链反应表明，从原位导管癌进展到浸润性癌再到淋巴结转移的过程中，组织蛋白酶抑制因子的表达呈逐步降低趋势。乳腺癌中缺乏组织蛋白酶抑制因子表达似乎与无病生存期短有关，并支持组织蛋白酶抑制因子作为肿瘤侵袭性和转移潜能指标的功能。关于组织蛋白酶抑制因子基因调控的新研究为肿瘤细胞中组织蛋白酶抑制因子可能重新表达的潜在前景提供了证据。组织蛋白酶抑制因子作为参与肿瘤侵袭、转移和血管生成的肿瘤抑制基因，其功能可能不限于乳腺癌。
