Reduction of isoforms of 15-lipoxygenase (15-LOX)-1 and 15-LOX-2 in human breast cancer
Reduction of isoforms of 15-lipoxygenase (15-LOX)-1 and 15-LOX-2 in human breast cancer
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DOI：
10.1016/j.plefa.2006.01.009
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发表时间：
2006-04-01
影响因子：
3
通讯作者：
Mansel, RE
中科院分区：
文献类型：
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作者：
Jiang, WG;Watkins, G;Mansel, RE
15-脂氧合酶（15-LOX）属于结构和功能相关的非血红素铁双加氧酶家族。它有两种亚型，1型（白细胞型）和2型（表皮型），并将花生四烯酸转化为类花生酸，包括抗癌13-HODE。在目前的研究中，我们调查的15-LOX亚型在人乳腺癌（n = 120）和正常乳腺组织（n = 32）的表达，使用免疫组化和定量分析的基因转录。15-LOX-1和15-LOX-2均存在于正常乳腺上皮细胞和血管内皮细胞中。15-LOX-1和15-LOX-2的染色在乳腺癌细胞中明显较弱。采用定量分析，发现15-LOX-1和15-LOX 2：CK 19的比率在乳腺肿瘤组织中低于正常组织（分别为P = 0.05和P = 0.035）。虽然没有显着的相关性之间的异构体和淋巴结的状态和肿瘤分级，显着较低的比例15-LOX 2：CK 19被认为是在晚期乳腺肿瘤。发现15-LOX-2和15-LOX-1在发生转移的患者的肿瘤中均处于显著较低的水平（与保持无疾病的患者相比，15-LOX-2的P = 0.0018，15-LOX-1的P = 0.031），在死于乳腺癌相关原因的患者中（15-LOX-2和15-LOX-1分别与无疾病组相比P = 0.043和P = 0.020）。研究还表明，与ER阴性肿瘤相比，ER阳性肿瘤的15-LOX-2水平显著较低，但15-LOX-1水平不低（P = 0.031）。最后，该研究表明，15LOX 1：15LOX 2比率在预测临床结果方面具有很强的价值。发生转移、局部复发和死于乳腺癌的患者的比例显著低于未发生乳腺癌的患者（P = 0.0057、P = 0.0075、P = 0.0091）。总之，本研究报告了15-LOX的两种亚型15-LOX-1和15-LOX-2在人乳腺癌中的异常表达。这种减少与乳腺癌的疾病进展和不良临床结局相关。该研究还报告了15-LOX-2和乳腺肿瘤中雌激素受体状态之间的联系。15-脂氧合酶的两种异构体在乳腺癌中具有肿瘤抑制作用。(c)2006爱思唯尔有限公司保留所有权利。
15-lipoxygenase (15-LOX) belongs to the structurally and functionally related nonheme iron dioxygenases family. It has two isoforms, type-1 (leukocyte type) and type-2 (epidermis type) and converts arachidonic acid to eicosanoids including the anti-cancer 13-HODE. In the current study, we investigate the expression of both isoforms of 15-LOX in human breast cancer (n = 120) and normal mammary tissues (n = 32), using immunohistochemistry and quantitative analysis of the gene transcripts. Both 15-LOX-1 and 15-LOX-2 were found in normal mammary epithelial cells and in vascular endothelial cells. The staining of both l5-LOX-1 and 15-LOX-2 was markedly weaker in breast cancer cells. Using quantitative analysis, it was found that the 15-LOX-1 and 15-LOX2:CK19 ratios were lower in breast tumour tissues, compared with normal tissues (P = 0.05 and P = 0.035, respectively). Although no significant correlation was seen between either isoforms and nodal status and tumour grade, significantly lower ratio of 15-LOX2:CK19 was seen in late stage breast tumours. Both 15-LOX-2 and 15-LOX-1 were found to be at significantly lower levels in tumours from patients who developed metastasis (P = 0.0018 for 15-LOX-2 and P = 0.031 for 15-LOX-1, compared with patients who remained disease free), and in patients who died of breast cancer related causes (P = 0.043 and P = 0.020 vs disease-free group, for 15-LOX-2 and 15-LOX-1, respectively). It was also demonstrated that ER-positive tumours had significantly lower levels of 15-LOX-2, but not 15-LOX-1, compared with ER-negative tumours (P=0.031). Finally, the study has shown that the 15LOX1:15LOX2 ratio had a strong value in predicting clinical outcome. Patients who developed metastasis, local recurrence and died of breast cancer had significantly lower ratio compared with those who remained disease free (P = 0.0057, P = 0.0075, P = 0.0091, respectively). In conclusion, the current study reports aberrant expression of both isoforms of 15-LOX, 15-LOX-1 and 15-LOX-2, in human breast cancer. The reduction is correlated with the disease progression of breast cancer and a poor clinical outcome. The study has also reported a link between 15-LOX-2 and oestrogen receptor status in breast tumours. Both isoforms of 15-lipoxygenese have a tumour suppressing role in breast cancer. (c) 2006 Elsevier Ltd. All rights reserved.