Laboratories of Molecular and Cell Biology, University Hospital Bulovka, Prague, Czech Republic.
Int J Oncol. 2010 Jan;36(1):275-83.
Human proteinase inhibitor-9 (PI-9)/serpinB9 is an intracellular ovalbumin-family serpin with nucleocytoplasmic distribution which is expressed in certain normal cell types and cancer cells of different origin. Due to binding and inactivating of granzyme B (GrB), PI-9 can protect the cells from GrB-mediated apoptosis. High levels of PI-9 expression in certain cancer cells may contribute to their resistance against the immune mediated killing. So far, it is not known whether non-small cell lung cardinomas (NSCLCs) express PI-9 mRNA and a functional PI-9 protein. Herein we report for the first time that NSCLC cells express both PI-9 mRNA and protein and that there is a subset of NSCLC cells with upregulated PI-9 mRNA and protein expression. Futhermore, our work revealed that the PI-9 protein expressed in NSCLC cells can inhibit the active GrB. Finally, analysis of PI-9 mRNA expression in NSCLC tumours from surgically treated patients showed that the expression of this transcript is upregulated in the less-differentiated lung adenocarcinomas. We suggest, that the upregulated expression of PI-9 in NSCLC cells may serve to protect them from apoptosis induced by GrB.
人蛋白水解酶抑制剂-9（PI-9）/丝氨酸蛋白酶抑制剂 B9 是一种具有核质分布的细胞内卵清蛋白家族丝氨酸蛋白酶抑制剂，在某些正常细胞类型和不同来源的癌细胞中表达。由于与颗粒酶 B（GrB）结合并使其失活，PI-9 可以保护细胞免受 GrB 介导的凋亡。某些癌细胞中高水平的 PI-9 表达可能有助于它们对免疫介导的杀伤产生抵抗。到目前为止，尚不清楚非小细胞肺癌（NSCLCs）是否表达 PI-9 mRNA 和功能性 PI-9 蛋白。在此，我们首次报道 NSCLC 细胞表达 PI-9 mRNA 和蛋白，并且存在一组 NSCLC 细胞中 PI-9 mRNA 和蛋白表达上调。此外，我们的工作表明，NSCLC 细胞中表达的 PI-9 蛋白可以抑制活性 GrB。最后，对手术治疗的 NSCLC 肿瘤中 PI-9 mRNA 表达的分析表明，这种转录物在分化程度较低的肺腺癌中表达上调。我们认为，NSCLC 细胞中 PI-9 的表达上调可能有助于保护它们免受 GrB 诱导的凋亡。
