Wnt and hedgehog gene pathway expression in serous ovarian cancer.
Wnt and hedgehog gene pathway expression in serous ovarian cancer.
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DOI：
10.1097/igc.0b013e31821caa6f
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发表时间：
2011-08
期刊：
影响因子：
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通讯作者：
Teng NN
中科院分区：
文献类型：
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作者：
Schmid S;Bieber M;Zhang F;Zhang M;He B;Jablons D;Teng NN
卵巢癌具有非常异质的组织学分类，并且对相同等级和类型的治疗的反应不同。我们研究了Wnt和hedgehog（Hh）通路中的基因，这两条通路对胚胎发育至关重要，并在多种人类癌症的增殖中发挥关键作用。导致增殖的这些途径基因的变异可能在肿瘤进展和对治疗的反应的变异中起作用。使用实时聚合酶链反应，我们研究了16例原发性3级国际妇产科联盟III期浆液性卵巢癌样本的Wnt途径基因AXIN 2、成纤维细胞生长因子9和Hh途径基因表达，包括胶质瘤相关癌基因1、胶质瘤相关癌基因2、patched同源物1、patched同源物2、Indian Hedgehog（HH）、sonic HH和Smoothened，G蛋白偶联受体蛋白。正常卵巢上皮细胞系作为对照。我们发现在原发性肿瘤样品中通路组分和靶基因的上调变化很大，通路之间存在明显的串扰。Wnt靶基因AXIN 2在所有浆液性卵巢癌样本中的表达均增加。成纤维细胞生长因子9在所有肿瘤中也过表达，其中4种肿瘤的基因表达增加超过1000倍。Hh途径基因的表达差异很大。超过一半的肿瘤样本显示参与Hh信号传导或通路激活，通过转录因子和Hh配体的表达或通过印度HH/sonic HH和受体编码补丁同源物1/补丁同源物2的过表达。我们发现患者样本之间Wnt和Hh通路中涉及的基因的倍数表达存在很大差异。
Ovarian cancer has very heterogeneous histological classification, and response to therapy of the same grade and type varies. We studied genes in the Wnt and hedgehog (Hh) pathways, which are essential for embryonic development and which play critical roles in proliferation in a variety of human cancers. Variations in these pathway genes causing proliferation could play a role in the variation in tumor progression and response to therapy. Using real-time polymerase chain reaction, we studied 16 primary grade 3 International Federation of Gynecology and Obstetrics stage III serous ovarian cancer samples for expression of the Wnt pathway gene AXIN2, fibroblast growth factor 9, and Hh pathway gene expressions of glioma-associated oncogene 1, glioma-associated oncogene 2, patched homolog 1, patched homolog 2, Indian Hedgehog (HH), sonic HH, and Smoothened, a G protein–coupled receptor protein. Normal ovary epithelial cell line was used as control. We found wide variation of up-regulation of pathway component and target genes in the primary tumor samples and apparent cross talk between the pathways. AXIN2, a Wnt target gene, showed increased expression in all serous ovarian cancer samples. Fibroblast growth factor 9 was also overexpressed in all tumors with greater than1000-fold increase in gene expression in 4 tumors. Expression of Hh pathway genes varied greatly. More than half of the tumor samples showed involvement of Hh signaling or pathway activation either by expression of transcription factors and Hh ligands or by overexpression of Indian HH/sonic HH and the receptor-encoding patched homolog 1/patched homolog 2. We found a wide variation in fold expression of genes involved in the Wnt and Hh pathway between patient samples.