Peroxisome proliferator activated receptor-γ (PPAR-γ) mediates the action of gamma linolenic acid in breast cancer cells

Jiang, Wen Guo; Redfern, Amanda; Bryce, Richard; Mansel, Robert Edward

doi:10.1054/plef.1999.0131

Cited by 74 publications

(47 citation statements)

References 34 publications

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“…Independent studies have shown that induction of COX-2 and inactivation of PPARg occurred during the development and progression of human breast carcinoma (Jiang et al, 2000;Ristimaki et al, 2002). On the other hand, inhibition of COX-2 and activation of PPARg has been shown to prevent mammary carcinogenesis in experimental animals (Suh et al, 1999;Harris et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Inhibition of COX-2 and activation of PPARg inhibited the development of rat mammary gland carcinogenesis (Suh et al, 1999;Harris et al, 2000). Additionally, independent studies showed that COX-2 and PPARg are induced and inactivated, respectively, in human breast carcinoma (Jiang et al, 2000;Ristimaki et al, 2002). Inoue et al (2000) proposed that expression of COX-2 was regulated by a negative feedback loop mediated through PPARg in macrophages.…”

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confidence: 99%

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Clinical implication of expression of cyclooxygenase-2 and peroxisome proliferator activated-receptor γ in epithelial ovarian tumours

et al. 2004

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Expression of cyclooxygenase (COX)-2 plays a key role in tumorigenesis and development and peroxisome proliferator-activated receptor g (PPARg) has been implicated in the control of COX-2 expression in some tissues. The aim of this study is to investigate (1) whether expression of COX-2 and PPARg is associated with ovarian carcinogenesis and progression of ovarian tumours and (2) whether COX-2 expression is controlled through ligand-mediated activation of PPARg in ovarian carcinoma cells. For this purpose, the presence of COX-2 and PPARg was immunohistochemically examined in 71 epithelial ovarian carcinomas, 18 borderline tumours and 23 benign tumours and the levels of COX-2 and PPARg proteins were determined by enzyme immunoassay in four benign tumours, three borderline tumours and 12 carcinomas. The frequency of COX-2 and PPARg detection was significantly increased and decreased as lesions progressed to carcinoma, respectively. The COX-2 protein was not detected in the three borderline tumours, whereas PPARg protein was detected in all of them. COX-2 protein was detected in eight of the 12 carcinomas, whereas PPARg protein was detected in only two cases. In addition, PPARg protein was not detected in all of the eight carcinomas in which COX-2 protein was detected, suggesting that expression of PPARg and COX-2 was in a reciprocal relationship. Furthermore, in cultured ovarian carcinoma cells, Western blot revealed that PPARg and COX-2 expression was regulated conversely as a result of stimulation by 15-deoxy-D 12, 14 PGJ 2 (15-PGJ 2 ), a PPARg activator. In addition, 15d-PGJ 2 suppressed tumour necrosis factor-ainduced-COX-2 expression, confirming the reciprocal correlation between COX-2 and PPARg. From these results, it was suggested that PPARg activation might suppress COX-2 expression via the nuclear factor-kB pathway in the ovarian carcinoma cells and that low expression of PPARg and high expression of COX-2 might be involved in carcinogenesis and progression of ovarian tumours.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Clinical implication of expression of cyclooxygenase-2 and peroxisome proliferator activated-receptor γ in epithelial ovarian tumours

et al. 2004

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“…26 We and others have shown that polyunsaturated fatty acids, such as gamma linolenic acid and eicosapentaenoic acid can activate PPAR␥ in cancer cells. 24,25,[27][28][29] In breast tissue, PPAR␥ agonist, together with RXR agonist, have a chemopreventative effect in preneoplastic lesions 30 and can prevent carcinogenesis in a rat model. 31 PPAR␥ agonist can inhibit the proliferation of breast cancer.…”

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confidence: 99%

Expression of peroxisome‐proliferator activated receptor‐gamma (PPARγ) and the PPARγ co‐activator, PGC‐1, in human breast cancer correlates with clinical outcomes

Jiang

Douglas-Jones

Mansel

2003

Intl Journal of Cancer

154

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Peroxisome-proliferator activated receptor-gamma (PPAR␥) belongs to a family of nuclear receptors and acts as receptor for peroxisome-proliferators, steroids, retinoic acids, and polyunsaturated fatty acids. Our study examined the transcript levels of peroxisome-proliferator activated receptorgamma (PPAR␥) and its co-activator (PGC-1) in a cohort of patients with breast cancer. An invasive breast cancer cell, MDA MB 231 exhibited lower level of expression of PPAR␥, compared to non-invasive MCF-7. Breast cancer tissues (n ‫؍‬ 120) exhibited a lower level of PPAR␥ mRNA compared to normal tissues (n ‫؍‬ 25, p ‫؍‬ 0.05). No difference, however, was seen with PGC-1. Although the levels of PPAR␥ and PGC-1 did not correlate with nodal involvement and grade, significantly lower levels of PPAR␥ were seen in TNM3 and TNM4 tumors and from patients with local recurrence and those who died of breast cancer. Lowest level of PGC-1 was also seen in TNM3 and TNM4 tumors and patients who died of breast cancer. We conclude that there is aberrant expression of PPAR␥ and its co-activator, PGC-1, in human breast cancer and low levels of these molecules in cancer tissues are associated with poor clinical outcomes. Peroxisome proliferator activator receptor-gamma (PPAR␥) belongs to a nuclear hormone receptor superfamily that regulates gene expression. 1-3 PPAR␥ contain DNA, lipid and A/B binding domains that recognize DNA response elements in the promoters of their target genes and interact with lipid ligands 4 and prostaglandins (PG J2). 5,6 Ligands for PPAR␥ such as troglitazone, BRL 49653, 15S-hydroxyeicosatetraenoic acid , and 15-deoxy-Delta 12,14-prostaglandin J2 have been shown to inhibit the growth of tumors and induce apoptosis of cancer cells, 7-10 and inhibit colon tumorigenesis in animal models. 11-14 PPAR␥ forms a complex with the PPAR␥ coactivators (PGC-1 and PGC-2) 21,22 and, together with other transcription factors SRC-1 and the CREB binding protein, 23 regulates gene expression, including cyclin regulator p27kip1, cMET protooncogene, and E-cadherin. The inhibition of cell growth by PPAR␥ agonists appears to be via multiple ways, including the inhibition of cyclin D1 15 and increase the level of cell cycle inhibitor P27 kip1 . 16 The proliferation of cancer cells that express PPAR␥ can be inhibited by its ligands and, interestingly, that the effect can be further enhanced by 9-cis retinoic acid, a ligand of RXR alpha. 17 PPAR␥ agonists can also reduce the growth and progressive activities of prostate cancer cells 18,19 and inhibit transcription of genes that are involved in tumor progression, such as the HGF receptor, cMET. 20 Abnormalities in PPAR family members have been implicated in tumorigenesis in animal models and in human cancers. PPAR␣ has been shown to be overexpressed in human prostate cancer. 24,25 Mutation of PPAR␥ has also been reported on colorectal cancer. PPAR␥ can be upregulated by agents such as butyrate in cancer cells. 26 We and others have shown that polyunsaturated fatty acids, such as gamma linol...

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“…Como exemplo disso, um estudo importante revelou que o GLA exerce seu efeito através do PPAR-γ, ou seja, inibindo esse receptor o GLA perde sua ação antitumoral sobre células de câncer de mama (Jiang et al, 2000). Através da ativação do PPARγ verificou-se a inibição do crescimento celular e indução da expressão de proteínas pró-apoptóticas como Bax e Bad, levando à morte de células de glioma humano (U87 e A172), sendo que as células primárias de astrócitos tratadas com o agonista desse PPAR não sofreram indução à morte celular (Zander et al, 2002).…”

Section: Processos Ligados à Angiogênese Invasão E Migraçãounclassified

“…Esses resultados sugerem que o GLA pode estar atuando na regulação transcricional via PPAR-γ in vivo, uma vez que o RNAm do nm23β, o qual é regulado transcricionalmente pelo PPAR-γ (Jiang et al, 2000), também se mostrou diminuído após o tratamento. Além disso, o PPAR-γ é capaz de interferir no fator nuclear de células T ativadas (NFAT) (Chung et al, 2003), o que pode levar a uma diminuição da expressão de COX-2.…”

Section: Mecanismo De Ação Do Gla Sobre O Controle Do Ciclo Celular Eunclassified

Análise da expressão de proteínas envolvidas no controle do ciclo celular, apoptose, angiogênese, invasão e migração de células C6 in vitro e in vivo, após o tratamento com o ácido g-linolênico (GLA) e com um novo complexo dirutênico contendo Ibuprofeno (Ru-Ibp).

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Tese apresentada ao Instituto de Ciências Biomédicas da Universidade de São Paulo, para obtenção do Título de Doutor em Ciências (Biologia Celular e Tecidual). São Paulo 2008MARCEL BENADIBA ANÁLISE DA EXPRESSÃO DE PROTEÍNAS ENVOLVIDAS NO CONTROLE DO CICLO CELULAR, APOPTOSE, ANGIOGÊNESE, INVASÃO E MIGRAÇÃO DE CÉLULAS C6 IN VITRO E IN VIVO, APÓS O TRATAMENTO COM O ÁCIDO γ-LINOLÊNICO (GLA) E COM UM NOVO COMPLEXO DIRUTÊNICO CONTENDO IBUPROFENO (Ru-Ibp)Tese apresentada ao Instituto de Ciências Biomédicas da Universidade de São Paulo, para obtenção do Título de Doutor em Ciências. Área de concentração: Biologia Celular e TecidualOrientador: Profa. Dra. Alison Colquhoun São Paulo 2008Aos irmãos da mesinha de caridade pelos conselhos e direcionamentos espirituais.Aos meus queridos pais Moses e Rosa pelo eterno amor, carinho e incentivo que nunca me faltaram.Aos meus queridos irmãos Felix e Vidal pelo carinho, apoio e compreensão.À minha querida esposa Alisan pela companhia, respeito, paciência e sincero amor.Aos meus futuros filhos. AGRADECIMENTOSÀ Karina Lawrence Ramos em especial os meus sinceros agradecimentos, pois sem ela eu não estaria aqui. Além do fato de me apresentar à Profa. Alison, sua paciência e atenção nos momentos mais difíceis do início das pesquisas ainda na iniciação científica foram cruciais para meu progresso no Doutorado.À minha orientadora e segunda mãe Alison Colquhoun, que com sua humildade e paciência admiráveis me ensinou a ser o cientista apaixonado que hoje sou. Que apesar das dificuldades no mundo da pesquisa, não desanima nunca! Muito Obrigado Chefe! Ao professor Dr. Jarbas Arruda Bauer pelo espaço em seu laboratório, respeito, risadas, conversas construtivas e pelas maravilhosas aulas que presenciei, das quais, com certeza, lembrarei sempre que estiver dando aula.Às professoras Dra. Marília Cerqueira Leite Seelaender e Dra. Marinilce Fagundes dos Santos pelo importante acolhimento e agradabilíssima convivência.À Profa. Dra. Denise de Oliveira Silva e à Dra. Geise Ribeiro do Instituto de Química da USP pela colaboração.Ao Prof. Dr. Rui Curi e à Dra. Thais Martins de Lima do Departamento de Fisiologia e Biofísica do ICB-USP pela colaboração.Aos meus colegas de laboratório: Fábio Luiz Tavares (que com muita paciência me ajudou nos meus primeiros PCRs), Fio (por todos os momentos que passamos no laboratório, incluindo nos finais de semana), Juliano Andreoli Myialke (pelos favores, paciência, palavras e pelas gargalhadas contagiantes e inconfundíveis), Camila Sommerauer Franchim (pelas incontáveis ajudas, gargalhadas, conversas e muito mais...), Luiz Carnevali Junior (pela amizade e companheirismo em diversos momentos), Emília Ribeiro (pela paciência e compreensão) e às recentes estagiárias Débora e Renata, que apesar do pouco tempo que estão no laboratório já considero grandes amigas.À Celiana, Bete e Heloísa pelo indispensável apoio administrativo.Ao pessoal da Biblioteca do Instituto de Ciências Biomédicas pela atenção e exemplo profissional.Ao pessoal do Xerox, pela eficiência, paciência e...

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Peroxisome proliferator activated receptor-γ (PPAR-γ) mediates the action of gamma linolenic acid in breast cancer cells

Cited by 74 publications

References 34 publications

Clinical implication of expression of cyclooxygenase-2 and peroxisome proliferator activated-receptor γ in epithelial ovarian tumours

Clinical implication of expression of cyclooxygenase-2 and peroxisome proliferator activated-receptor γ in epithelial ovarian tumours

Expression of peroxisome‐proliferator activated receptor‐gamma (PPARγ) and the PPARγ co‐activator, PGC‐1, in human breast cancer correlates with clinical outcomes

Análise da expressão de proteínas envolvidas no controle do ciclo celular, apoptose, angiogênese, invasão e migração de células C6 in vitro e in vivo, após o tratamento com o ácido g-linolênico (GLA) e com um novo complexo dirutênico contendo Ibuprofeno (Ru-Ibp).

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