Expression of hypoxia-inducible factor-1α, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma: Correlation with poor prognosis with possible regulation

Kotaro Miyake, Tomoharu Yoshizumi, Satoru Imura, Koji Sugimoto, Erdenebulgan Batmunkh, Hirofumi Kanemura, Yuji Morine, Mitsuo Shimada

Research output: Contribution to journalArticlepeer-review

134 Citations (Scopus)

Abstract

OBJECTIVES: Hypoxia-inducible factor 1α (HIF-1α) is a transcription factor that plays an important role in tumor growth and metastasis. Inhibition of histone deacetylase shows a marked inhibition of HIF-1α expression; however, the association between HIF-1α and histone deacetylase 1 (HDAC1), metastasis-associated protein 1 (MTA1) is not fully understood. METHODS: Hypoxia-inducible factor 1α, HDAC1, and MTA1 expressions were detected by immunohistochemistry in 39 pancreatic carcinoma patients. The correlations between the expression of HIF-1α, HDAC1, or MTA1 and clinical features and the prognosis were analyzed. RESULTS: Hypoxia-inducible factor 1α, HDAC1, and MTA1 positive stainings were found in 41%, 56%, and 31%, respectively. There was no correlation between HIF-1α, HDAC1, or MTA1 expression levels and any clinical parameters. The survival rate for patients with HIF-1α and HDAC1-positive stainings were significantly lower than for patients with HIF-1α 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-1α expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis for pancreatic carcinoma and indicates that HIF-1α and HDAC1/MTA1 are a promising therapeutic target in pancreatic carcinoma treatment.

Original languageEnglish
Pages (from-to)e1-e9
JournalPancreas
Volume36
Issue number3
DOIs
Publication statusPublished - Apr 1 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

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