Sager R, Sheng S, Pemberton P, Hendrix M J
Division of Cancer Genetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Adv Exp Med Biol. 1997;425:77-88.
Maspin, a serpin found in mammary epithelial cells, has been shown to have tumor suppressor activity. The gene is expressed in normal human mammary epithelial cells but down-regulated in invasive breast carcinomas. Similar patterns of expression at the RNA and protein levels are seen by Northern analysis with cells grown in culture and by immunostaining of tissues. Biological assays of invasion by tumor cells through Matrigel membranes and of motility have shown that recombinant maspin inhibits both processes, and that its inhibitory action is totally lost by a single cleavage at the reaction center. Tumor transfectants expressing maspin are inhibited in growth and metastasis in nude mice. Maspin is located in the cell membrane and extracellular matrix, and does not behave as a classical inhibitory serpin against any known target protease. Its mode of action is presently unknown.
Maspin是一种在乳腺上皮细胞中发现的丝氨酸蛋白酶抑制剂,已被证明具有肿瘤抑制活性。该基因在正常人类乳腺上皮细胞中表达,但在浸润性乳腺癌中下调。通过对培养细胞进行Northern分析以及对组织进行免疫染色,在RNA和蛋白质水平上观察到了类似的表达模式。肿瘤细胞通过基质胶膜的侵袭和运动性的生物学测定表明,重组maspin抑制这两个过程,并且其抑制作用在反应中心单次切割后完全丧失。表达maspin的肿瘤转染子在裸鼠中的生长和转移受到抑制。Maspin位于细胞膜和细胞外基质中,对任何已知的靶蛋白酶都不表现为经典的抑制性丝氨酸蛋白酶抑制剂。其作用方式目前尚不清楚。