NDLI: Plasminogen activator inhibitor-2 (PAI-2) overexpression supports bladder cancer development in PAI-1 knockout mice in N-butyl-N- (4-hydroxybutyl)-nitrosamine- induced bladder cancer mouse model

Content Provider	Springer Nature : BioMed Central
Author	Furuya, Hideki Hayashi, Kazukuni Shimizu, Yoshiko Kim, Nari Tsukikawa, Yutaro Chen, Runpu Sun, Yijun Chan, Owen T. M. Pagano, Ian Peres, Rafael Hokutan, Kanani Igari, Fumie Chan, Keith S. Rosser, Charles J.
Abstract	Background Accumulating evidence suggests that plasminogen activator inhibitor-1 (PAI-1) plays an important role in bladder tumorigenesis by regulating cell cycle. However, it remains unclear whether and how inhibition of PAI-1 suppresses bladder tumorigenesis. Methods To elucidate the therapeutic effect of PAI-1 inhibition, we tested its tumorigenicity in PAI-1 knockout (KO) mice exposed to a known bladder carcinogen. Results PAI-1 deficiency did not inhibit carcinogen-induced bladder cancer in mice although carcinogen-exposed wild type mice significantly increased PAI-1 levels in bladder tissue, plasma and urine. We found that PAI-1 KO mice exposed to carcinogen tended to upregulate protein C inhibitor (PAI-3), urokinase-type plasminogen activator (uPA) and tissue-type PA (tPA), and significantly increased PAI-2, suggesting a potential compensatory function of these molecules when PAI-1 is abrogated. Subsequent studies employing gene expression microarray using mouse bladder tissues followed by post hoc bioinformatics analysis and validation experiments by qPCR and IHC demonstrated that SERPING1 is further downregulated in PAI-1 KO mice exposed to BBN, suggesting that SERPING1 as a potential missing factor that regulate PAI-2 overexpression (compensation pathway). Conclusions These results indicate that serpin compensation pathway, specifically PAI-2 overexpression in this model, supports bladder cancer development when oncoprotein PAI-1 is deleted. Further investigations into PAI-1 are necessary in order to identify true potential targets for bladder cancer therapy.
Related Links	https://translational-medicine.biomedcentral.com/counter/pdf/10.1186/s12967-020-02239-6.pdf
Ending Page	12
Page Count	12
Starting Page	1
File Format	HTM / HTML
ISSN	14795876
DOI	10.1186/s12967-020-02239-6
Journal	Journal of Translational Medicine
Issue Number	1
Volume Number	18
Language	English
Publisher	BioMed Central
Publisher Date	2020-02-05
Access Restriction	Open
Subject Keyword	Biomedicine Medicine Public Health Plasminogen activator inhibitor-1 (PAI-1) knockout mouse PAI-1 PAI-2 Serine protease inhibitors Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology Medicine
Journal Impact Factor	6.1/2023
5-Year Journal Impact Factor	6.3/2023

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EFFECT OF PROTEASE INHIBITORS IN MICE TREATED WITH THE HEPATOCARCINOGEN, HEXACHLOROCYCLOHEXANE (α-ISOMER) AND THE BLADDER CARCINOGEN, N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE

N-butyl-N-(4-hydroxybutyl) Nitrosamine Induced Bladder Cancer in Mice

Cytogenetic characterization of an N-butyl-N-(4-hydroxybutyl) nitrosamine-induced mouse papillary urothelial carcinoma

Effect of protease inhibitors in mice treated with the hepatocarcinogen, hexachlorocyclohexane (alpha-isomer) and the bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine.

The dynamics of the inflammatory response during BBN-induced bladder carcinogenesis in mice

INHIBTORY EFFECTS OF COMBINATION CHEMOTHERAPEUTIC REGIMENS ON MOUSE BLADDER CARCINOGENESIS INDUCED BY N-BUTYL-N-(4-HYDROXYBUTYL) NITROSAMINE

Significance of overexpression of metallothionein in mouse urinary bladder focal lesions induced by treatment with N-butyl-N-(4-hydroxybutyl)-nitrosamine

Biodistribution of gold nanoparticles in BBN-induced muscle-invasive bladder cancer in mice

EFFECTS OF VARIOUS CHEMICALS ON THE DEVELOPMENT OF MOUSE URINARY BLADDER TUMORS INDUCED BY N-BUTYL-N-(4-HYDROXYBUTYL) NITROSAMINE

Plasminogen activator inhibitor-2 (PAI-2) overexpression supports bladder cancer development in PAI-1 knockout mice in N-butyl-N- (4-hydroxybutyl)-nitrosamine- induced bladder cancer mouse model

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Plasminogen activator inhibitor-2 (PAI-2) overexpression supports bladder cancer development in PAI-1 knockout mice in N-butyl-N- (4-hydroxybutyl)-nitrosamine- induced bladder cancer mouse model