The α folate receptor is highly activated in malignant pleural mesothelioma
The α folate receptor is highly activated in malignant pleural mesothelioma
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DOI：
10.1067/mtc.2001.111176
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发表时间：
2001-02-01
影响因子：
6
通讯作者：
Sugarbaker, D
中科院分区：
文献类型：
--
作者：
Bueno, R;Appasani, K;Sugarbaker, D
目的：确定叶酸受体基因在恶性胸膜间皮瘤中是否过度表达。方法：对从正常肺、胸膜和间皮瘤中获得的新鲜冷冻RNA进行差异显示分析。鉴定并表征了 60 个差异表达基因。与正常组织相比，在间皮瘤中过度表达的一种基因是人类α叶酸受体。使用根据叶酸受体序列设计的反义探针对 61 例恶性胸膜间皮瘤患者（33 例上皮瘤和 28 例混合瘤或肉瘤样瘤）的冰冻切片进行原位杂交。对照包括正常胸膜、正常肺癌、其他癌症以及所有肿瘤的感觉对照。还进行了叶酸受体探针的 Northern 分析和抗 α 叶酸受体抗体的免疫组织化学分析。 结果：与对照组织相比，61 个间皮瘤中有 44 个 (72%) 的叶酸受体 mRNA 表达量高出 2 至 4 倍。肿瘤的组织学类型不影响叶酸受体激活率。 Northern分析和免疫组织化学实验证实了这些发现。结论：与正常邻近组织相比，大多数间皮瘤肿瘤过度表达α叶酸受体蛋白。这一发现可能有助于解释抗叶酸药物在治疗间皮瘤方面具有活性的观察结果。它还鼓励进一步研究这种恶性肿瘤中叶酸受体相关的治疗策略。
Objective: To determine whether the folate receptor gene is overexpressed in malignant pleural mesothelioma.Methods: Differential display analysis was performed with fresh frozen RNA obtained from normal lung, pleura, and mesothelioma. Sixty differentially expressed genes were identified and characterized. One gene that was overexpressed in mesothelioma versus normal tissue was the human alpha folate receptor. In situ hybridization with antisense probes designed on the basis of the sequence of the folate receptor was performed with frozen sections from 61 patients (33 epithelial and 28 mixed or sarcomatoid tumors) with malignant pleural mesothelioma. The controls included normal pleura, normal lung, other cancers, and sense controls for all of the tumors. Northern analysis with a folate receptor probe and immunohistochemical analysis with anti-alpha folate receptor antibodies were also performed.Results: Forty-four (72%) of the 61 mesothelioma tumors were found to have between 2-fold and 4-fold higher mRNA expression of the folate receptor when compared with the control tissues. The histologic type of the tumor did not affect the rate of folate receptor activation. Northern analysis and immunohistochemical experiments confirmed these findings.Conclusions: A majority of mesothelioma tumors examined overexpress the alpha folate receptor protein when compared with normal adjacent tissues. This finding may help explain the observations that antifolate drugs have activity in the treatment of mesothelioma. It also encourages further study of folate receptor-related treatment strategies in this malignancy.