Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-γ and levels of prostaglandin E2 and 15-deoxy-Δ12.14-prostaglandin J2 in human breast cancer and metastasis
Expression of cyclooxygenase-2 and peroxisome proliferator-activated receptor-γ and levels of prostaglandin E2 and 15-deoxy-Δ12.14-prostaglandin J2 in human breast cancer and metastasis
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DOI：
10.1002/ijc.10770
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发表时间：
2003-01-01
影响因子：
6.4
通讯作者：
Badr, MZ
中科院分区：
文献类型：
--
作者：
Badawi, AF;Badr, MZ
环氧合酶-2 （COX-2）表达和过氧化物酶体增殖物活化受体- γ (PPARgamma)失活与人类乳腺癌风险增加有关。我们的研究目的是研究COX-2（与由此产生的前列腺素E-2、PGE(2)）和PPARgamma(及其天然内源性配体15-Deoxy-Delta(12,14)-前列腺素J（2)、15d-PGJ(2)）在人类乳腺癌发展和转移过程中不同阶段的关系。人类乳腺组织标本取自正常乳房或纤维囊性疾病患者，并作为对照（n = 22）。同时还收集了乳腺癌患者未受累区（n = 25）、肿瘤区（n = 25）和淋巴结转移区（n = 15）的组织。与对照组相比，癌症患者组织中COX-2和PPARgamma mRNA的表达分别升高和下调。与非转移组织相比，转移组织有更高的改变（p < 0.05）。COX-2和PPAR-y表达的改变与组织中PGE水平的升高(2)和15d-PGJ水平的降低(2)相一致。PGE(2)与15-d-PGJ(2)呈显著负相关（r = -0.51, p < 0.05）。COX-2与PPAR-y mRNA呈负相关（r = -0.72）， PGE与COX-2呈正相关（r = 0.68）， p < 0.05。COX-2 mRNA表达和PGE水平升高(2)，PPAR-y mRNA表达和15d-PGJ水平下调(2)被认为是乳腺癌风险的预测因子（p < 0.05）。我们的研究结果表明，COX-2和PPARgamma表达的改变以及随后组织中PGE(2)和15-d-PGJ(2)水平的调节可能影响人类乳腺癌的发展及其转移的进展。(C) 2002 Wiley-Liss, Inc。
Cyclooxygenase-2 (COX-2) expression and peroxisome proliferator-activated receptor-gamma (PPARgamma) inactivation are linked to increased risk of human breast cancer. The purpose of our study was to examine the relationship between COX-2 (with the resulting prostaglandins E-2, PGE(2)) and PPARgamma (and its natural endogenous ligand 15-Deoxy-Delta(12,14)- prostaglandin J(2), 15d-PGJ(2)) at various stages during the development of human breast cancer and its progression to metastasis. Human breast tissue specimens were collected from normal breasts or from individuals with fibrocystic disease and served as controls (n = 22). Tissues were also collected from uninvolved (n = 25), tumor (n = 25) and lymph node metastasis (n = 15) regions from breast cancer patients. COX-2 and PPARgamma mRNA expression were increased and down-regulated, respectively, in tissues from cancer patients compared to controls. Metastatic tissues tended to have higher alterations compared to non-metastatic tissues (p < 0.05). These altered expressions in COX-2 and PPAR-y were paralleled by increases in the tissue levels of PGE(2) and decreases in 15d-PGJ(2). A significant inverse correlation was found between PGE(2) and 15-d-PGJ(2) (r = -0.51, p < 0.05). Significant correlations (p < 0.05) were also obtained between COX-2 and PPAR-y mRNA (inverse, r = -0.72) and between COX-2 and PGE(2) (direct, r = 0.68). Increases in COX-2 mRNA expression and levels of PGE(2), and down-regulation of PPAR-y mRNA expression and 15d-PGJ(2) levels were characterized as predictors of breast cancer risk (p < 0.05). Our results suggest that the altered expression of COX-2 and PPARgamma and the subsequent modulation in the tissue levels of PGE(2) and 15-d-PGJ(2) may influence the development of human breast cancer and its progression to metastasis. (C) 2002 Wiley-Liss, Inc.