Kimura Shigeru, Kitadai Yasuhiko, Kuwai Toshio, Tanaka Shinji, Hihara Jun, Yoshida Kazuhiro, Toge Tetsuya, Chayama Kazuaki
Department of Medicine and Molecular Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Pathobiology. 2005;72(4):179-85. doi: 10.1159/000086787.
Hypoxia-inducible factor (HIF)-1 is important in the control of transcription of several genes related to angiogenesis. We have previously reported that expression of HIF-1alpha correlates with venous invasion and clinical outcome in esophageal squamous cell carcinoma. p53 has been reported to interact with HIF-1alpha and induce ubiquitin-mediated proteosomal degradation of HIF-1alpha. The purpose of this study was to clarify whether the expression of p53 is associated with that of HIF-1alpha.
Expression of p53, HIF-1alpha and vascular endothelial growth factor (VEGF) was examined in 81 archival surgical specimens of human esophageal squamous cell carcinoma tissue. CD34 and single-stranded DNA were used to evaluate angiogenesis and apoptosis.
Forty-seven of the 81 (58.0%) tumor specimens showed high levels of nuclear p53 immunoreactivity. Overexpression of p53 was observed in the early clinical stage of tumor development. Expression of p53 was not correlated with HIF-1alpha or VEGF expression, angiogenesis or apoptosis in esophageal carcinoma.
These results suggest that mutations in p53 play a role in carcinogenesis but not in the progression of esophageal squamous cell carcinoma. HIF-1alpha may not only be regulated by p53 but also by other factors.
缺氧诱导因子（HIF）-1在调控多个与血管生成相关基因的转录过程中起重要作用。我们之前报道过，HIF-1α的表达与食管鳞状细胞癌的静脉侵袭及临床预后相关。据报道，p53可与HIF-1α相互作用，并诱导HIF-1α通过泛素介导的蛋白酶体降解。本研究旨在阐明p53的表达是否与HIF-1α的表达相关。
对81份人食管鳞状细胞癌组织的存档手术标本检测p53、HIF-1α和血管内皮生长因子（VEGF）的表达。采用CD34和单链DNA评估血管生成和细胞凋亡。
81份肿瘤标本中有47份（58.0%）显示核p53免疫反应性高水平。在肿瘤发展的临床早期观察到p53的过表达。在食管癌中，p53的表达与HIF-1α或VEGF的表达、血管生成或细胞凋亡均无相关性。
这些结果表明，p53突变在致癌过程中起作用，但在食管鳞状细胞癌进展过程中不起作用。HIF-1α可能不仅受p53调控，还受其他因素调控。
