Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy
Patched and smoothened mRNA expression in human astrocytic tumors inversely correlates with histological malignancy
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DOI：
10.1023/a:1019660421216
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发表时间：
2002-09-01
影响因子：
3.9
通讯作者：
Kamiguchi, H
中科院分区：
文献类型：
--
作者：
Katayama, M;Yoshida, K;Kamiguchi, H
Patched蛋白（Ptc）是超音hedgehog基因（Shh）的跨膜受体，与另一种跨膜蛋白smoothened （Smo）功能相关。Ptc是肿瘤抑制基因，而Smo是神经外胚层肿瘤的原癌基因。它们的下游分子Gli1、Gli2和Gli3是胶质母细胞瘤的致癌基因。我们分析了Ptc、Smo和Gli家族成员在人类星形细胞肿瘤中的mRNA表达。采用实时聚合酶链反应定量测定40例肿瘤（弥漫性星形细胞瘤、间变性星形细胞瘤6例、胶质母细胞瘤12例、22例）和4个星形细胞瘤衍生细胞系的mRNA表达。免疫组化法检测肿瘤的mb -1增殖细胞指数（pci）。与世界卫生组织（WHO）的分类相比，Ptc和Smo mrna的数量随着组织学恶性肿瘤的进展成比例地减少，在星形细胞肿瘤衍生细胞系中也获得了类似的结果。然而，各基因mRNA表达水平与MIB-1 pci之间无显著相关性。2例患者Gli1 mRNA表达水平变化较大，表达水平均呈高表达。两例临床及组织学均未见明显特点。总之，我们的研究结果表明Ptc和Smo mRNA水平与组织学恶性肿瘤呈负相关，表明这些基因产物与星形细胞肿瘤的抑制有关。相比之下，Gli家族成员的mRNA水平与组织学恶性肿瘤之间没有显著相关性，这表明Gli蛋白与星形细胞肿瘤的进展无关。
Patched (Ptc) is a transmembrane receptor for sonic hedgehog (Shh) and functionally associated with another transmembrane protein, smoothened (Smo). Ptc is a tumor suppressor gene whereas Smo serves as a proto-oncogene of neuroectodermal tumors. Their downstream molecules, Gli1, Gli2, and Gli3, are oncogenes of glioblastomas. We have analyzed mRNA expression of Ptc, Smo, and Gli family members in human astrocytic tumors. The mRNA expression was quantified by real-time polymerase chain reactions in 40 tumors (diffuse astrocytomas; 6 cases: anaplastic astrocytomas; 12 cases: glioblastomas; 22 cases) and four cell lines derived from astrocytic tumors. The MIB-1 proliferating cell indices (PCIs) of these tumors were analyzed by immunohistochemistry. In comparison with the World Health Organization (WHO) classification, the amount of Ptc and Smo mRNAs decreased in proportion to the progression of histological maliganancy, and similar results were obtained with astrocytic tumor-derived cell lines. However, there was no remarkable correlation between the mRNA expression level of each gene and the MIB-1 PCIs. The mRNA expression level of Gli1 was variable and highly elevated in two cases. No remarkable features were found clinically or histologically in these two cases.In summary, our results indicate that Ptc and Smo mRNA levels have an inverse correlation with histological malignancy and suggest that these gene products are implicated in the suppression of astrocytic tumors. In contrast, there was no significant correlation between the mRNA levels of the Gli family members and histological malignancy, suggesting that Gli proteins are not associated with the progression of astrocytic tumors.