Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low‐ and high‐grade prostatic intraepithelial neoplasia and prostatic carcinoma

Baltacı, Sümer; Orhan, Dıclehan; Göğüş, Çağatay; Türkölmez, Kadír; Tulunay, Özden; Göğüş, Orhan

doi:10.1046/j.1464-410x.2001.02231.x

Cited by 83 publications

(70 citation statements)

References 21 publications

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“…These authors suggested that sex hormones may be involved in iNOS induction and that there may be a role for NO in the pathogenesis in BPH. Baltaci et al [12] also suggested that NO generated by iNOS may be involved in prostate cell growth, including BPH, prostatic intraepithelial neoplasia and prostate cancer. NO is closely associated with prostate carcinogenesis because of its role in cytotoxicity and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

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Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

Yoo¹,

Kim²,

Chung³

et al. 2010

Asian J Androl

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The precise aetiology of benign prostatic hyperplasia (BPH) remains unclear; however, it is known that immunological inflammatory processes have a role in the pathogenesis of BPH initiation and progression. Nitric oxide synthase 2 (NOS2) inducible expression is closely correlated with prostatic disease, including prostate cancer and BPH. The aim of this study was to investigate the relationship between NOS2 polymorphisms and BPH. With a cohort of 205 controls and 229 BPH subjects, we genotyped three single nucleotide polymorphisms (SNPs) in the NOS2 gene, including rs2779248 (promoter, −278 T/C), rs10459953 (5′-untranslated region) and rs2297518 (exon 16, missense, Ser608Leu), using direct sequencing and restriction fragment length polymorphism. The genotypic and allelic frequencies between control and BPH subjects were compared, and the associations among the BPH subjects were analyzed. SNPStats, SNPAnalyzer and HelixTree programmes were used to analyze SNPs. There was no association on SNPs between control and BPH subjects. When BPH subjects were analyzed, there was no association on SNPs between the low and high prostate-specific antigen groups. However, one SNP (rs10459953, odds ratio [OR] = 0.44, 95% confidence interval [CI] = 0.29-0.65, P < 0.0001, in codominant model; OR = 0.23, 95% CI = 0.12-0.46, P < 0.0001, in dominant model; and OR = 0.46, 95% CI = 0.24-0.86, P = 0.015, in recessive model) was associated with prostatic volume in BPH. We detected a strong association in genotype frequencies of NOS2 SNP (rs10459953) between subjects with small and large prostatic volume in BPH. The result suggests that NOS2 may be associated with prostatic volume in BPH.

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Section: Discussionmentioning

confidence: 99%

“…The expression of iNOS has been investigated in prostatic diseases, such as prostate cancer, prostatic intraepithelial neoplasia and BPH [12][13][14]. It is not detected in normal prostatic tissue; however, it is expressed in most BPH tissue, even in the absence of chronic prostatitis.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

Yoo¹,

Kim²,

Chung³

et al. 2010

Asian J Androl

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show abstract

“…Baltaci et al reported that the expression of iNOS was higher in highgrade PIN and prostatic carcinoma samples than in benign prostatic hypertrophy and low-grade PIN samples. These findings suggest that nitric oxide produced by iNOS may be involved in prostate tumorigenesis (53). In addition, Calvisi et al revealed that iNOS and NADPH oxidase were involved in ROS generation during c-Myc/transforming growth factor a hepatocarcinogenesis and were inhibited by antioxidant agent treatment (54).…”

Section: Mol Cancer Res 2008;6(2) February 2008mentioning

confidence: 95%

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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“…Células benignas luminais podem ser induzidas a expressar GSTP1 face ao desenvolvimento do estresse oxidativo. Epitélio prostático maligno, no entanto, quase invariavelmente não expressa GSTP1 devido à ilha de hipermetilação CpG na região promotora do gene GSTP1 (Palapattu et al, 2004;Wang et al, 2009 (Baltaci et al, 2001).…”

Section: Introductionunclassified

Óxido nítrico, GSTP-1 e p53: qual o papel desses biomarcadores nas lesões prostáticas do cão?

Croce¹,

Rodrigues²,

Faleiro

et al. 2011

Arq. Bras. Med. Vet. Zootec.

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 RESUMOConfeccionou-se um microarranjo de tecido (TMA) com 146 amostras de lesões prostáticas caninas. Este continha 17,2% de hiperplasia prostática benigna (HPB), 32,4% de atrofia inflamatória proliferativa (PIA), 2,6% de prostatite, 8,6% de focos de neoplasia intraepitelial prostática (PIN), 29,1% de carcinomas e 9,3% de próstatas normais. Cortes histológicos sequenciais foram feitos e utilizados para reação de imunoistoquímica com os anticorpos primários anti-p-53, anti-NOS-2 e anti-GSTP. Avaliou-se de cada core o escore de células marcadas para cada anticorpo utilizado. Os resultados foram tabulados por grupo diagnóstico e submetidos ao teste Tuckey. Os carcinomas prostáticos do cão e a PIA apresentaram maior número de amostras (41) com mais de 75% das células positivas para NOS-2, demonstrando a influência do estresse oxidativo no desenvolvimento dessas lesões. As próstatas normais e as afecções desta glândula, HPB, PIA, PIN, prostatite e carcinoma, expressaram a proteína GSTP-1, o que conferiu proteção ao tecido prostático canino a danos oxidativos. A proteína p53 estava presente em todas as amostras estudadas, incluindo o tecido prostático normal, porém as lesões prostáticas apresentaram maior número de amostras com escores mais elevados de marcação (escores três e quatro), presente em 95% dos focos de PIA e carcinoma. Concluiu-se que o aumento de expressão de óxido nítrico nas lesões prostáticas no cão e a expressão de GSTP-1 podem ter protegido o tecido prostático canino e que a expressão de p53 foi positiva e uniforme nas próstatas normais e com lesões hiperplásicas e displásicas.Palavras-chave: cão, próstata, imunoistoquímica, óxido nítrico, GSTP-1, p53

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Inducible nitric oxide synthase expression in benign prostatic hyperplasia, low‐ and high‐grade prostatic intraepithelial neoplasia and prostatic carcinoma

Cited by 83 publications

References 21 publications

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

Nitric oxide synthase 2 gene polymorphisms are associated with prostatic volume in Korean men with benign prostatic hyperplasia

Angiotensin II Induces Oxidative Stress in Prostate Cancer

Óxido nítrico, GSTP-1 e p53: qual o papel desses biomarcadores nas lesões prostáticas do cão?

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