Relationship of hypoxia-inducible factor 1α and p21WAF1/CIP1 expression to cell apoptosis and clinical outcome in patients with gastric cancer

被引:21
作者
Mizokami K. [1 ]
Kakeji Y. [1 ]
Oda S. [1 ]
Maehara Y. [1 ]
机构
[1] Department of Surgery and Science, Graduate School of Medical Science, Kyushu University, Fukuoka
关键词
Gastric Cancer; Apoptotic Index; Increase Cell Survival; Lower Apoptotic Index; Resected Tissue Specimen;
D O I
10.1186/1477-7819-4-94
中图分类号
学科分类号
摘要
Background: Hypoxia-inducible factor- 1α (HIF- 1α) plays an essential role in oxygen homeostasis. The exporession of HIF-1α-inducible genes is associated with tumor progression. p21 mediates cell cycle arrest and is one of the downstream genes targeted by HIF-1. Patients and methods: We examined the relationship between HIF-1α and p21 expression, apoptosis and tumor progression using tissue specimens obtained surgically from 126 patients with gastric cancer. Results: Immunohistochemical analysis indicated that loss of p21 expression correlated positively with patient age and tumor size. Lymph node metastasis was significantly more frequent in tumors with loss of p21 expression (P =0.022). HIF-1α-positive/p21-negative tumors had a lower apoptotic index than any other tumor samples, and patients with HIF-1α-positive/p21-negative tumors also had a significantly poorer prognosis than the other patient populations. Conclusion: These results suggest that loss of HIF-1α-dependent p21 expression results in decreased apoptosis, increased cell survival and more aggressive tumors. © 2006 Mizokami et al; licensee BioMed Central Ltd.
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共 31 条
[1]  
Semenza G.L., Regulation of mammalian O2 homeostasis by hypoxia-inducible factor I, Annu Rev Cell Dev Biol, 15, pp. 551-578, (1999)
[2]  
Semenza G.L., HIF-1 and human disease: One highly involved factor, Genes Dev, 14, pp. 1983-1991, (2000)
[3]  
Griffiths E.A., Pritchard S.A., Welch I.M., Price P.M., West C.M., Is the hypoxia-inducible factor pathway important in gastric cancer?, Eur J Cancer, 41, pp. 2792-2805, (2005)
[4]  
Graeber T.G., Osmanian C., Jacks T., Housman D.E., Koch C.J., Lowe S.W., Giaccia A.J., Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours, Nature, 379, pp. 88-91, (1996)
[5]  
el-Deiry W.S., Tokino T., Velculescu V.E., Levy D.B., Parsons R., Trent J.M., Lin D., Mercer W.E., Kinzier K.W., Vogelstein B., WAFI, a potential mediator of p53 tumor suppression, Cell, 75, pp. 817-825, (1993)
[6]  
Salnikow K., Costa M., Figg W.D., Blagosklonny M.V., Hyperinducibility of Hypoxia-responsive Genes without p53/p21-dependent Checkpoint in Aggressive Prostate Cancer, Cancer Res, 60, pp. 5630-7113, (2000)
[7]  
Carmeliet P., Dor Y., Herbert J.M., Fukumura D., Brusselmans K., Dewerchin M., Neeman M., Bono F., Abramovitch R., Maxwell P., Koch C.J., Ratcliffe P., Moons L., Jain R.K., Collen D., Keshert E., Keshet E., Role of HIF-1 alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis, Nature, 394, pp. 485-490, (1998)
[8]  
Japanese classification of gastric carcinoma, 12, (1995)
[9]  
Zhong H., De Marzo A.M., Laughner E., Lim M., Hilton D.A., Zagzag D., Buechler P., Isaacs W.B., Semenza G.L., Simons J.W., Overexpression of Hypoxia-inducible Factor 1 {{alpha}} in Common Human Cancers and Their Metastases, Cancer Res, 59, pp. 5830-7113, (1999)
[10]  
Noda H., Maehara Y., Irie K., Kakeji Y., Yonemura T., Sugimachi K., Growth pattern and expressions of cell cycle regulator proteins p53 and p21WAF1/CIP1 in early gastric carcinoma, Cancer, 92, pp. 1828-1835, (2001)