Expression of hypoxia-inducible factor-1α, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma

被引:148
作者
Miyake, Kotaro [1 ]
Yoshizumi, Tomoharu [1 ]
Imura, Satoru [1 ]
Sugimoto, Koji [1 ]
Batmunkh, Erdenebulgan [1 ]
Kanemura, Hirofumi [1 ]
Morine, Yuji [1 ]
Shimada, Mitsuo [1 ]
机构
[1] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Surg, Tokushima 7708503, Japan
关键词
hypoxia-inducible factor 1 alpha; histone deacetylase 1; metastasis-associated protein 1; pancreatic carcinoma; immunohistochemistry;
D O I
10.1097/MPA.0b013e31815f2c2a
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Objectives: Hypoxia-inducible factor 1 alpha (HIF-1 alpha) is a transcription factor that plays an important role in tumor growth and metastasis. Inhibition of histone deacetylase shows a marked inhibition of HIF1 alpha expression; however, the association between HIF-1 alpha and histone deacetylase 1 (HDAC1), metastasis-associated protein 1 (MTA1) is not fully understood. Methods: Hypoxia-inducible factor 1 alpha, HDAC1, and MTA1 expressions were detected by immunohistochemistry in 39 pancreatic carcinoma patients. The correlations between the expression of HIF-1 alpha, HDAC1, or MTA1 and clinical features and the prognosis were analyzed. Results: Hypoxia-inducible factor 1 alpha, HDAC1, and MTA1 positive stainings were found in 41%, 56%, and 31%, respectively. There was no correlation between HIF-1 alpha, HDAC1, or MTA1 expression levels and any clinical parameters. The survival rate for patients with HIF-1 alpha and HDAC1-positive stainings were significantly lower than for patients with HIF-1 alpha and HDAC1-negative stainings. The MTA1 overexpression group did not have a significantly lower prognosis than the MTA1 underexpression group. The survival rate for the HDAC1(+)/MTA1(2-3) group was significantly lower than for the other groups. Conclusions: These results suggest that HIF-1 alpha expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis for pancreatic carcinoma and indicates that HIF-1 alpha and HDAC1/MTA1 are a promising therapeutic target in pancreatic carcinoma treatment.
引用
收藏
页码:E1 / E9
页数:9
相关论文
共 51 条
[1]  
Aebersold DM, 2001, CANCER RES, V61, P2911
[2]  
Birner P, 2000, CANCER RES, V60, P4693
[3]  
Birner P, 2001, CLIN CANCER RES, V7, P1661
[4]   How Avastin potentiates chemotherapeutic drugs - Action and reaction in antiangiogenic therapy [J].
Blagosklonny, MV .
CANCER BIOLOGY & THERAPY, 2005, 4 (12) :1307-1310
[5]   Levels of hypoxia-inducible factor-1α independently predict prognosis in patients with lymph node negative breast carcinoma [J].
Bos, R ;
van der Groep, P ;
Greijer, AE ;
Shvarts, A ;
Meijer, S ;
Pinedo, HM ;
Semenza, GL ;
van Diest, PJ ;
van der Wall, E .
CANCER, 2003, 97 (06) :1573-1581
[6]   Levels of hypoxia-inducible factor-1α during breast carcinogenesis [J].
Bos, R ;
Zhong, H ;
Hanrahan, CF ;
Mommers, ECM ;
Semenza, GL ;
Pinedo, HM ;
Abeloff, MD ;
Simons, JW ;
van Diest, PJ ;
van der Wall, E .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2001, 93 (04) :309-314
[7]   Mi-2/NuRD: multiple complexes for many purposes [J].
Bowen, NJ ;
Fujita, N ;
Kajita, M ;
Wade, PA .
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION, 2004, 1677 (1-3) :52-57
[8]  
Brizel DM, 1996, CANCER RES, V56, P941
[9]   Hypoxia-inducible factor 1 regulates vascular endothelial growth factor expression in human pancreatic cancer [J].
Büchler, P ;
Reber, HA ;
Büchler, M ;
Shrinkante, S ;
Büchler, MW ;
Friess, H ;
Semenza, GL ;
Hines, OJ .
PANCREAS, 2003, 26 (01) :56-64
[10]   Clinical development of histone deacetylase inhibitors as anticancer agents [J].
Drummond, DC ;
Noble, CO ;
Kirpotin, DB ;
Guo, ZX ;
Scott, GK ;
Benz, CC .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2005, 45 :495-528