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缺氧诱导因子-1α、Bax、Bcl-xL和P53在人类结直肠癌中的累积表达

Cumulative expression of HIF-1-alpha, Bax, Bcl-xL and P53 in human colorectal cancer.

作者信息

Wincewicz Andrzei, Sulkowska Mariola, Koda Mariusz, Sulkowski Stanislaw

机构信息

Department of Pathology, Medical University of Bialystok, Bialystok, Poland.

出版信息

Pathology. 2007 Jun;39(3):334-8. doi: 10.1080/00313020701329765.

Abstract

AIMS AND METHODS

Hypoxia-inducible factor (HIF-1) which contains oxygen regulated HIF-1alpha subunit maintains cytoprotective defence against hypoxic injury by induction of numerous genes. However, apoptotic regulators such as Bcl-xL, Bax and P53 have not been associated with HIF-1 dependent regulation in immunohistochemical evaluation of human colorectal cancer tumours so far. Thus, we visualised these proteins immunohistochemically and using Spearman's test compared for the first time their expression in regard to different clinicopathological traits in 123 (113 for P53 evaluation) human colorectal cancers.

RESULTS

HIF-1alpha correlated with Bcl-xL or Bax in all patients and particularly in node negative and node positive cancers, deeper intramural tumours (pT3+pT4) and adenocarcinomas. There was no significance in a small group of tumours with lesser extent through intestinal walls (pT1+pT2). In addition HIF-1alpha associated with Bcl-xL in mucinous cancers. Moreover, HIF-1alpha correlated with Bcl-xL or Bax in moderately (G2) and poorly differentiated (G3) cancers, rectal and colonic tumours and in different sex and age groups. P53 correlated only with Bax exclusively in younger patients.

CONCLUSIONS

HIF-1alpha may influence expression of Bax or Bcl-xL, at least indirectly, as correlations between HIF-1alpha and Bax or Bcl-xL occur constantly.

摘要

目的与方法

缺氧诱导因子(HIF-1)包含受氧调节的HIF-1α亚基,通过诱导众多基因维持对缺氧损伤的细胞保护防御。然而,在人类结直肠癌肿瘤的免疫组织化学评估中,凋亡调节因子如Bcl-xL、Bax和P53尚未与HIF-1依赖性调节相关联。因此,我们采用免疫组织化学方法检测这些蛋白,并首次使用Spearman检验比较了它们在123例(P53评估为113例)人类结直肠癌中不同临床病理特征下的表达情况。

结果

在所有患者中,尤其是在无淋巴结转移和有淋巴结转移的癌症、壁内浸润较深的肿瘤(pT3 + pT4)和腺癌中,HIF-1α与Bcl-xL或Bax相关。在一小部分肠壁浸润程度较轻的肿瘤(pT1 + pT2)中无显著相关性。此外,在黏液癌中HIF-1α与Bcl-xL相关。而且,在中度(G2)和低分化(G3)癌症、直肠和结肠肿瘤以及不同性别和年龄组中,HIF-1α与Bcl-xL或Bax相关。仅在年轻患者中P53仅与Bax相关。

结论

HIF-1α可能至少间接影响Bax或Bcl-xL的表达,因为HIF-1α与Bax或Bcl-xL之间持续存在相关性。

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