MASPIN, A SERPIN WITH TUMOR-SUPPRESSING ACTIVITY IN HUMAN MAMMARY EPITHELIAL-CELLS

MASPIN, A SERPIN WITH TUMOR-SUPPRESSING ACTIVITY IN HUMAN MAMMARY EPITHELIAL-CELLS
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DOI:
10.1126/science.8290962
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发表时间:
1994-01-28
期刊:
影响因子:
56.9
通讯作者:
SAGER, R
SAGER, R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
ZOU, ZQ;ANISOWICZ, A;SAGER, R

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编码蛋白酶抑制剂丝氨酸蛋白酶抑制剂家族相关蛋白的基因被鉴定为可能在人类乳腺癌中起作用的候选肿瘤抑制基因。该基因产物称为maspin,在正常乳腺上皮细胞中表达,但在大多数乳腺癌细胞系中不表达。用maspin基因转染MDA-MB-435乳腺癌细胞在体外没有改变细胞的生长特性,但降低了细胞在裸鼠中诱导肿瘤和转移的能力,以及在体外通过基底膜基质侵入的能力。对人类乳腺癌标本的分析显示,maspin表达的缺失最常发生在晚期癌症中。这些结果支持了maspin作为肿瘤抑制因子发挥作用的假设。
A gene encoding a protein related to the serpin family of protease inhibitors was identified as a candidate tumor suppressor gene that may play a role in human breast cancer. The gene product, called maspin, is expressed in normal mammary epithelial cells but not in most mammary carcinoma cell lines. Transfection of MDA-MB-435 mammary carcinoma cells with the maspin gene did not alter the cells' growth properties in vitro, but reduced the cells' ability to induce tumors and metastasize in nude mice and to invade through a basement membrane matrix in vitro. Analysis of human breast cancer specimens revealed that loss of maspin expression occurred most frequently in advanced cancers. These results support the hypothesis that maspin functions as a tumor suppressor.