Overexpression of group II phospholipase A2 in human breast cancer tissues is closely associated with their malignant potency.

Overexpression of group II phospholipase A2 in human breast cancer tissues is closely associated with their malignant potency.
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DOI:
10.1038/bjc.1994.229
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发表时间:
1994-06
影响因子:
8.8
通讯作者:
Ogawa, M.
Ogawa, M.
中科院分区:
医学1区
文献类型:
--
作者:
Yamashita, S.-I.;Yamashita, J.-I.;Ogawa, M.

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膜相关磷脂酶A2(M-PLA2)是一种水解磷酸甘油酯sn-2脂肪酰基酯键的酶。我们用最近发展起来的一种特异的放射免疫分析方法,测定了325例人类乳腺癌组织提取液中M-PLA2的浓度。M-PLA2的组织浓度与临床病理因素的相关性分析表明,有远处转移者的M-PLA2酶水平明显高于无远处转移者。此外,硬化性癌中M-PLA2的浓度显著高于其他组织学类型。未发现M-PLA2浓度与年龄、月经状况、肿瘤大小、组织学分级、血管受累或雌激素受体(ER)和孕激素受体(PR)状态有关。应用免疫组织化学方法检测了纤维腺瘤、IV期乳腺癌及其皮肤转移灶中M-PLA2基因的表达。Northern印迹分析显示,乳腺癌原发灶和转移灶中均有一条清晰的M-PLA2杂交条带,而纤维腺瘤中有一条微弱的杂交条带。在另一项研究中确定,在5 ng 100 mg-1蛋白的临界点上,M-PLA2浓度高的乳腺癌患者的无病生存期和总生存期明显短于那些M-PLA2浓度低的患者。在多因素分析中,M-PLA2被发现是乳腺癌复发和死亡的独立预后因素。讨论了M-PLA2在人乳腺癌组织中表达的可能意义。
Membrane-associated phospholipase A2 (M-PLA2) is an enzyme that hydrolyses the sn-2 fatty acyl ester bond of phosphoglycerides. We measured M-PLA2 concentration in tissue extracts from 325 human breast cancers using a specific radioimmunoassay recently developed. Correlation analyses between the tissue concentration of M-PLA2 and clinicopathological factors showed that the enzyme level was significantly higher in patients with distant metastasis than in those without. In addition, M-PLA2 concentration was significantly higher in scirrhous carcinoma than in other histological types. No significant association was found between M-PLA2 concentration and age, menstrual status, tumour size, histological grade, vessel involvement or oestrogen receptor (ER) and progesterone receptor (PR) status. The expression of M-PLA2 mRNA was examined in a fibroadenoma, a stage IV breast cancer and its metastatic site of skin. Northern blot analysis showed a clear hybridisation band corresponding to M-PLA2 mRNA in both primary breast cancer and its metastatic site, while the fibroadenoma expressed a faint band corresponding to M-PLA2 mRNA. Breast cancer patients with high M-PLA2 concentrations exhibited significantly shorter disease-free and overall survival than those with low M-PLA2 concentration at the cut-off point of 5 ng 100 mg-1 protein, which was determined in a separate study. In multivariate analysis, M-PLA2 was found to be an independent prognostic factor for disease recurrence and death in human breast cancer. The possible significance of M-PLA2 expression in human breast cancer tissue is discussed.
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