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Smoothened在胰腺癌和结直肠癌中的核定位与过表达

Nuclear localization and Overexpression of Smoothened in Pancreatic and Colorectal Cancers.

作者信息

Niyaz Madiha, Khan Mosin S, Wani Rauf A, Shah Omar J, Besina Syed, Mudassar Syed

机构信息

Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India.

Department of General and Minimal Invasive Surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India.

出版信息

J Cell Biochem. 2019 Jul;120(7):11941-11948. doi: 10.1002/jcb.28477. Epub 2019 Feb 19.

Abstract

Smoothened (SMO) is a significant signalling protein which functions as a key transducer for the hedgehog signalling pathway, an important signalling mechanism with key roles in development and oncogenesis. The correlation of expression dynamics of SMO with pancreatic and colorectal cancer genesis has been known but with ambiguity. Therefore, in this study, we investigated messenger RNA (mRNA) and protein expression of SMO in pancreatic and colorectal cancers in our population and assessed relationship with various clinicopathological parameters. Surgically resected tumour and adjacent histologically normal tissues from 33 and 61 pancreatic and colorectal cancer patients were investigated in the present study. Expression of SMO was analysed by quantitative real-time polymerase chain reaction and immunohistochemistry. At mRNA level, SMO was overexpressed in 72.72% (24 of 33) and 50.81% (31 of 61) of the pancreatic and colorectal cancer cases as compared with their adjacent normal tissues. SMO immunohistochemical analysis revealed nuclear localization and overexpression was observed in 51.51% (17 of 33) and 40.98% (25 of 61) of pancreatic and colorectal cancer tissues. SMO overexpression was significantly associated with smoking, late-stage disease and lymph node metastasis in patients with Colorectal cancer. Our results showed that SMO is dysregulated in pancreatic and colorectal cancers and may be considered as a target in cancer therapeutics.

摘要

smoothened(SMO)是一种重要的信号蛋白,作为刺猬信号通路的关键转导器发挥作用,该信号通路是一种在发育和肿瘤发生中起关键作用的重要信号机制。SMO表达动态与胰腺癌和结直肠癌发生的相关性已为人所知,但尚不明确。因此,在本研究中,我们调查了我们研究人群中胰腺癌和结直肠癌中SMO的信使核糖核酸(mRNA)和蛋白表达,并评估了其与各种临床病理参数的关系。本研究调查了33例胰腺癌患者和61例结直肠癌患者手术切除的肿瘤及相邻组织学正常组织。通过定量实时聚合酶链反应和免疫组织化学分析SMO的表达。在mRNA水平上,与相邻正常组织相比,72.72%(33例中的24例)的胰腺癌病例和50.81%(61例中的31例)的结直肠癌病例中SMO过表达。SMO免疫组织化学分析显示细胞核定位,在51.51%(33例中的17例)的胰腺癌组织和40.98%(61例中的25例)的结直肠癌组织中观察到过表达。在结直肠癌患者中,SMO过表达与吸烟、疾病晚期和淋巴结转移显著相关。我们的结果表明,SMO在胰腺癌和结直肠癌中表达失调,可能被视为癌症治疗的一个靶点。

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