The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung
The expression of fatty acid synthase (FASE) is an early event in the development and progression of squamous cell carcinoma of the lung
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DOI：
10.1053/hupa.2000.9842
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发表时间：
2000-09-01
期刊：
影响因子：
3.3
通讯作者：
Grizzle, WE
中科院分区：
文献类型：
--
作者：
Piyathilake, CJ;Frost, AR;Grizzle, WE
脂肪酸合成酶（FASE）水平升高与某些癌症晚期的相关性已引起人们注意，这种酶可能是预后不良的标志。由于最近的研究表明，癌细胞依赖于脂肪酸合成活性，并且这种酶的药理学抑制剂对癌细胞具有选择性细胞毒性，因此FASE的表达也可能为肿瘤过程的干预提供潜在的靶点。为了确定FASE在肺肿瘤过程中表达的潜在用途，我们用化学方法评价了其在60例肺鳞状细胞癌（SCC）和相关“癌前病变”的存档标本中的表达模式，并与其在60例非癌标本的正常支气管上皮中的表达进行了比较。FASE在SCC相关的未受累支气管上皮中的表达（平均值= 0.40 ± 0.03，中位数= 0.38）显著高于其在非癌标本支气管上皮中的表达（平均值= 0.18 ± 0.02，中位数= 0.16），表明其早期表达。我们还观察到FASE表达从SCC相关的未受累支气管上皮（平均值= 0.40 +/- 0.03，中位数= 0.38）到上皮增生（0.58 +/- 0.04，中位数= 0.57）再到SCC（1.53 +/- 0.06，中位数= 1.50）呈统计学显著性逐步增加。结果提示FASE的表达是肺鳞癌发生发展的早期事件。抑制脂肪酸合成的作用。代谢类似物的酶功能可能是治疗SCC的有用策略。FASE在早期病变如SCC相关的未受累支气管上皮和上皮增生中的表达也可能提供一种潜在的手段，用于在肺肿瘤过程中的早期干预，甚至防止其恶性转化为浸润性癌。Copyright（C）2000 by W.B.桑德斯公司
Correlation of elevated levels of the lipogenic enzyme, fatty acid synthase (FASE), with advanced stages of some cancers has drawn attention to this enzyme as a possible marker of poor prognosis. Because recent studies have shown that cancer cells are dependent on fatty acid synthetic activity and pharmacologic inhibitors of this enzyme are selectively cytotoxic to cancer cells, expression of FASE also may provide a potential target for intervention in the neoplastic process.:To determine the potential usefulness of expression of FASE in the neoplastic process of the lung, we evaluated its pattern of expression immunohistochemically in archival specimens from 60 human lung specimens with squamous cell cancer (SCC) and associated "preneoplastic" lesions compared with its expression in the normal bronchial epithelium of 60 noncancer specimens. The expression of FASE was significantly big-her in SCC associated uninvolved bronchial epithelium (mean = 0.40 +/- 0.03, median = 0.38) compared with its expression in the bronchial epithelium of noncancer specimens (mean = 0.18 +/- 0.02, median = 0.16) indicating its early expression. We also observed a statistically significant step-wise increase in FASE expression from SCC associated uninvolved bronchial epithelium (mean = 0.40 +/- 0.03, median = 0.38) to epithelial hyperplasia (0.58 +/- 0.04, median = 0.57) to SCC (1.53 +/- 0.06, median = 1.50). The results suggested that expression of FASE is an early event in the development and progression of SCC of the lung. The inhibition of fatty acid synthesis by inhibiting. enzymatic function with metabolic analogues may be a useful strategy in the treatment of SCCs. The expression of FASE in early lesions such as SCC associated uninvolved bronchial epithelium and epithelial hyperplasia might also provide a potential means for intervention early in the neoplastic process in the lung or even preventing their malignant transformation to invasive carcinomas. Copyright (C) 2000 by W.B. Saunders Company.