Expression of proteinase inhibitor-9/serpinB9 in non-small cell lung carcinoma cells and tissues.
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.
Rousalova
Ilona
I
Laboratories of Molecular and Cell Biology, University Hospital Bulovka, Prague, Czech Republic.
Krepela
Evzen
E
Prochazka
Jan
J
Cermak
Jan
J
Benkova
Kamila
K
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053804:Granzymes / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000096:biosynthesis*
D011480:Protease Inhibitors; D012333:RNA, Messenger; C102316:SERPINB9 protein, human; D015843:Serpins; D053804:Granzymes