Neuroserpin (PI‐12) is upregulated in high‐grade prostate cancer and is associated with survival

Hasumi, Hisashi; Ishiguro, Hitoshi; Nakamura, Masashi; Sugiura, Shinpei; Osada, Yutaka; Miyoshi, Yasuhide; Fujinami, Kiyoshi; Yao, Masahiro; Hamada, Kenji; Yamada-Okabe, Hisafumi; Kubota, Yoshinobu; Uemura, Hiroji

doi:10.1002/ijc.20967

Cited by 22 publications

(18 citation statements)

References 22 publications

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“…The liplin-a2 gene was down-regulated by dihydrotestosterone in prostate cancer cells, and the nmt55 gene was up-regulated in prostate cancer tissue (2,3). Also, we found that neuroserpin (protease inhibitor 12) expression was higher in prostate cancer than in normal prostate tissue by GeneChip analysis (4). Although numerous investigators have examined and identified genes related to prostate cancer, the mechanisms of prostate cancer development and progression remain obscure.…”

Section: Introductionmentioning

confidence: 59%

Angiotensin II Induces Oxidative Stress in Prostate Cancer

Uemura

Ishiguro

et al. 2008

Molecular Cancer Research

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Angiotensin II has been shown to be a cytokine especially acting as a growth factor. A local renin-angiotensin system has been identified in the prostate gland, and the physiologic function of angiotensin II seems to be similar in prostate cancer, as we previously reported. In the present study, we explored the biological role of angiotensin II in oxidative stress of prostate cancer cells. Activated Akt was determined, and the expression of oxidative stress-related proteins (p47phox, manganese superoxide dismutase 2, glutathione peroxidase) was examined by Western blotting in LNCaP cells, which were stimulated with angiotensin II and/or an angiotensin II receptor type 1 blocker, candesartan. To examine DNA damage induced by angiotensin II, 8-hydroxy-2 ¶-deoxyguanosine was determined, and Western blots were analyzed to detect checkpoint proteins including p53, Chk2, and cdc2. Immunocytochemical studies of inducible nitric oxide synthase and superoxide anion radical (O 2 À ) were done in LNCaP cells stimulated with angiotensin II. The phosphorylation of Akt was induced by angiotensin II treatment and inhibited by candesartan, as well as by LY294002, an inhibitor of phosphoinositide 3-kinase. Oxidative stress-related proteins were up-regulated by angiotensin II and inhibited by pretreatment with candesartan or catalase. The level of 8-hydroxy-2 ¶-deoxyguanosine was increased by angiotensin II and conversely decreased by candesartan. Immunocytochemical studies showed that angiotensin II enhanced an inflammatory marker, inducible nitric oxide synthase, and the production of O 2 À radical. The hypothesis that angiotensin II has the potential to induce oxidative stress, which may be implicated in carcinogenesis of the prostate gland through long-term exposure to chronic inflammation is proposed. (Mol Cancer Res 2008;6(2):250 -8)

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Section: Introductionmentioning

confidence: 59%

Angiotensin II Induces Oxidative Stress in Prostate Cancer

Uemura

Ishiguro

et al. 2008

Molecular Cancer Research

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“…The possible mechanisms for increasing the synthesis of mutant neuroserpin in human FENIB patients are now thought as follows: (i) up-regulation of neuroserpin expression by various stresses and diseases such as transient cerebral ischemia, schizophrenia, and cancer (6,30,31); (ii) increased stability of neuroserpin mRNA by up-regulated expression of HuD, a neuron-specific mRNA stabilizing protein (32); and (iii) deficiency in ER quality control system (17). The fact that accumulation of G392E neuroserpin in CNS requires a threshold level of gene/ protein expression in transgenic mice suggests that the downregulation of mutant neuroserpin gene expression could be one approach by which we can delay or prevent the accumulation of G392E neuroserpin in CNS of FENIB patients harboring this type of mutation.…”

Section: Discussionmentioning

confidence: 99%

Mutation-, Aging-, and Gene Dosage-dependent Accumulation of Neuroserpin (G392E) in Endoplasmic Reticula and Lysosomes of Neurons in Transgenic Mice

Kato²,

Takasawa³

et al. 2008

Journal of Biological Chemistry

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Mutations in human neuroserpin gene cause an autosomal dementia, familial encephalopathy with neuroserpin inclusion bodies (FENIB). We generated and analyzed transgenic mice expressing high levels of either FENIB-type (G392E) or wildtype human neuroserpin in neurons of the central nervous system. G392E neuroserpin accumulated age-dependently in neurons of the neocortex, thalamus, amygdala, pons, and spinal cord of homozygous transgenic mice. Such accumulations were not observed in hemizygous transgenic mice nor in transgenic mice for wild-type neuroserpin. In differential centrifugation of brain homogenates, G392E neuroserpin recovered in the nucleus-rich fraction dramatically increased along with aging, suggesting that the aggregations gradually increase their densities presumably by their conversion into heavier and more compact configurations. In immunoelectron microscopical analyses, immunopositivities for G392E neuroserpin were found not only in endoplasmic reticulum but also in lysosomes. G392E neuroserpin transgenic mice were much more susceptible to seizures induced by kainate administration than nontransgenic mice. Overall, G392E neuroserpin accumulated in the central nervous system neurons of transgenic mice in mutation-, aging-, and gene dosage-dependent manners. The established transgenic mice will be valuable to elucidate not only mechanisms for the formation of G392E neuroserpin aggregations but also pathways for the degradation and/or clearance of the already formed aggregations in neurons.

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“…All specific quantities were divided by the quantity of b-actin as previously reported. 11,12 Statistical analysis…”

Section: Evaluation Of Responsementioning

confidence: 99%

Pilot study of angiotensin II receptor blocker in advanced hormone-refractory prostate cancer

et al. 2005

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Neuroserpin (PI‐12) is upregulated in high‐grade prostate cancer and is associated with survival

Cited by 22 publications

References 22 publications

Angiotensin II Induces Oxidative Stress in Prostate Cancer

Angiotensin II Induces Oxidative Stress in Prostate Cancer

Mutation-, Aging-, and Gene Dosage-dependent Accumulation of Neuroserpin (G392E) in Endoplasmic Reticula and Lysosomes of Neurons in Transgenic Mice

Pilot study of angiotensin II receptor blocker in advanced hormone-refractory prostate cancer

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