Increased p53 immunoreactivity in proliferative inflammatory atrophy of prostate is related to focal acute inflammation

Wang, Wanzhong; Bergh, Anders; Damber, Jan‐Erik

doi:10.1111/j.1600-0463.2008.00006.x

Cited by 18 publications

(25 citation statements)

References 42 publications

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“…The tumor suppressor p53 is overexpressed in PIA lesions as compared to normal-appearing prostatic acini (58). Moreover, a positive correlation betwen p53 expression and Ki-67 was found in COX-2-positive PIA lesions.…”

Section: Molecular Evidencementioning

confidence: 71%

Inflammation, prostatitis, proliferative inflammatory atrophy: ‘Fertile ground’ for prostate cancer development?

Perletti¹,

Montanari

Vral³

et al. 2009

Mol Med Rep

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Abstract. Inflammatory processes caused by chemical, physical or biological agents are known to be important cofactors in the pathogenesis of human cancer. In the prostate, epithelial tissue damage followed by cell regeneration in the presence of inflammation is believed to be a key event in neoplastic transformation. According to the 'injury and regeneration' model, inflammatory cells infiltrating the prostate release reactive species in response to bacterial/viral infection, uric acid, or dietary prostate carcinogens. Besides inducing inflammation, tissue injury by these and other agents would promote the appearance of proliferative inflammatory atrophy (PIA). A subset of proliferating atrophic cells -possibly showing stemcell features -may be exposed to the genotoxic insult of free radicals and to an increased rate of mutations and chromosomal aberrations, ultimately leading to neoplastic initiation, promotion and progression. In the last decade, the link between inflammation and cancer and the hypothesis pointing to PIA as a risk lesion for prostate cancer have been extensively investigated at the pre-clinical, clinical, morphological, cellular and molecular levels. In this article, recent reports describing supportive or negative evidence on the link between prostate inflammation, atrophy and cancer are schematically reviewed.

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Section: Molecular Evidencementioning

confidence: 71%

Inflammation, prostatitis, proliferative inflammatory atrophy: ‘Fertile ground’ for prostate cancer development?

Perletti¹,

Montanari

Vral³

et al. 2009

Mol Med Rep

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“…Como o número de amostras positivas para NOS-2 também foi alto, infere-se que o GSTP-1 esteja aumentado em resposta ao estresse oxidativo. Resultado semelhante foi relatado na literatura humana (Wang et al, 2009) (Wang et al, 2009).…”

Section: Discussionunclassified

“…Se o processo falhar, acionam-se eventos apoptóticos e há destruição da célula danificada (Schmitt, 1999;Wang et al, 2009). Em células normais, a proteína p-53, denominada tipo selvagem, tem meia-vida curta e não se acumula no tecido em concentrações detectáveis.…”

Section: Introductionunclassified

“…GSTP1 tem sido descrito como um gene "guardião", pois protege a célula ativamente de dano oxidativo do genoma mediado pelos componentes carcinogênicos (Palapattu et al, 2004;Wang et al, 2009). No epitélio prostático normal humano, a expressão de GSTP1 está geralmente confinada ao compartimento basal.…”

Section: Introductionunclassified

“…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

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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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Protection against oxidative DNA damage and stress in human prostate by glutathione S‐transferase P1

Kanwal

Pandey

Bhaskaran

et al. 2012

Molecular Carcinogenesis

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The pi-class glutathione S-transferase (GSTP1) actively protect cells from carcinogens and electrophilic compounds. Loss of GSTP1 expression via promoter hypermethylation is the most common epigenetic alteration observed in human prostate cancer. Silencing of GSTP1 can increase generation of reactive oxygen species (ROS) and DNA damage in cells. In this study we investigated whether loss of GSTP1 contributes to increased DNA damage that may predispose men to a higher risk of prostate cancer. We found significantly elevated (103%; P<0.0001) levels of 8-oxo-2′-deoxogunosine (8-OHdG), an oxidative DNA damage marker, in adenocarcinomas, compared to benign counterparts, which positively correlated (r=0.2) with loss of GSTP1 activity (34%; P<0.0001). Silencing of GSTP1 using siRNA approach in normal human prostate epithelial RWPE1 cells caused increased intracellular production of ROS and higher susceptibility of cells to H2O2-mediated oxidative stress. Additionally, human prostate carcinoma LNCaP cells, which contain a silenced GSTP1 gene, were genetically modified to constitutively express high levels of GSTP1. Induction of GSTP1 activity lowered endogenous ROS levels in LNCaP-pLPCX-GSTP1 cells, and when exposed to H2O2, these cells exhibited significantly reduced production of ROS and 8-OHdG levels, compared to vector control LNCaP-pLPCX cells. Furthermore, exposure of LNCaP cells to green tea polyphenols caused re-expression of GSTP1, which protected the cells from H2O2-mediated DNA damage through decreased ROS production compared to non-exposed cells. These results suggest that loss of GSTP1 expression in human prostate cells, a process that increases their susceptibility to oxidative stress-induced DNA damage, may be an important target for primary prevention of prostate cancer.

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Increased p53 immunoreactivity in proliferative inflammatory atrophy of prostate is related to focal acute inflammation

Cited by 18 publications

References 42 publications

Inflammation, prostatitis, proliferative inflammatory atrophy: ‘Fertile ground’ for prostate cancer development?

Inflammation, prostatitis, proliferative inflammatory atrophy: ‘Fertile ground’ for prostate cancer development?

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

Protection against oxidative DNA damage and stress in human prostate by glutathione S‐transferase P1

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