表皮型脂肪酸结合蛋白和脂肪酸合成酶在乳腺浸润性导管癌的表达及临床病理意义

Expression of epidermal fatty acid-binding protein and fatty acid synthase in infiltrating ductal breast carcinoma

目的探讨脂肪酸结合蛋白和脂肪酸合成酶与乳腺浸润性导管癌发生发展的关系及作用机制,以探询新的分子标志和早期分子治疗的靶基因。方法用半定量逆转录聚合酶链反应、免疫组织化学和Westernblot等方法检测表皮型脂肪酸结合蛋白(E-FABP)和脂肪酸合成酶(FAS)在76例浸润性乳腺导管癌中的表达变化。结果E-FABP广泛分布于浸润性导管癌的血管内皮细胞、导管和腺泡的上皮细胞,mRNA和蛋白质的表达量在III级浸润性导管癌的较I、II级明显下调(P<0.05)。FAS主要分布于腺泡和导管的上皮细胞,表达量随组织学级数的变化趋势与E-FABP相同,两者的表达具有明显相关性(P<0.05)。此外,E-FABP和FAS的表达与及组织学级数相关(P<0.05),与绝经情况、淋巴结转移、雌激素受体和孕激素受体无关(P>0.05)。结论在I、II级浸润性导管癌,E-FABP可能作为FAS的下游分子,结合和转运FAS合成的长链脂肪酸,以维持肿瘤细胞旺盛的代谢;在III级导管癌,E-FABP、FAS的表达明显下调,癌细胞的活动可能有赖于其他信号分子起作用。本研究为进一步探寻浸润性乳腺导管癌的分子标志及早期治疗途径提供理论依据。

Objective To detect the expression of epidermal fatty acid-binding protein （E-FABP） and fatty acid synthase （FAS） in human breast cancer and identify the potential markers and therapeutic targets for breast cancer. Methods FAS and E-FABP expressions were detected in 76 patients with infiltrating ductal breast carcinoma using RT-PCR, immnohistochemistry and Western blotting. The possible associations of the expression of the two proteins with the major clinicopathological factors were analyzed. Results E-FABP and FAS expression levels were significantly decreased （P〈0.05） in grade Ⅲ as compared with grades Ⅰ and Ⅱ infiltrating ductal breast carcinoma. There was a positive correlation between E-FABP and FAS expressions, but their expressions were not correlated to the clinicopathological factors o（ the patients except for the tumor grades. High E-FABP expression level in grades I and II tumors were associated with an early increased responsiveness to FAS. Conclusion The variation of the E-FABP and FAS expressions in the lesions is associated with increase of the risk for breast cancer, and the results of this study provide evidence for developing new molecular markers of high-risk lesions and identifying new the targets for breast cancer therapy.