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

Abstract

OBJECTIVES:

Hypoxia-inducible factor 1alpha (HIF-1alpha) is a transcription factor that plays an important role in tumor growth and metastasis. Inhibition of histone deacetylase shows a marked inhibition of HIF-1alpha expression; however, the association between HIF-1alpha and histone deacetylase 1 (HDAC1), metastasis-associated protein 1 (MTA1) is not fully understood.

METHODS:

Hypoxia-inducible factor 1alpha, HDAC1, and MTA1 expressions were detected by immunohistochemistry in 39 pancreatic carcinoma patients. The correlations between the expression of HIF-1alpha, HDAC1, or MTA1 and clinical features and the prognosis were analyzed.

RESULTS:

Hypoxia-inducible factor 1alpha, HDAC1, and MTA1 positive stainings were found in 41%, 56%, and 31%, respectively. There was no correlation between HIF-1alpha, HDAC1, or MTA1 expression levels and any clinical parameters. The survival rate for patients with HIF-1alpha and HDAC1-positive stainings were significantly lower than for patients with HIF-1alpha 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-1alpha expression may be regulated through HDAC1/MTA1, which is associated with a poor prognosis for pancreatic carcinoma and indicates that HIF-1alpha and HDAC1/MTA1 are a promising therapeutic target in pancreatic carcinoma treatment.

• Authors: Kotaro Miyake, Tomoharu Yoshizumi, Satoru Imura, Koji Sugimoto, Erdenebulgan Batmunkh, Hirofumi Kanemura, Yuji Morine, Mitsuo Shimada
• Journal: Pancreas (Pancreas) Vol. 36 Issue 3 Pg. e1-9 (Apr 2008) ISSN: 1536-4828 [Electronic] United States
• PMID: 18362831 (Publication Type: Journal Article)

Chemical References

• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Mta1 protein, human
• Repressor Proteins
• Trans-Activators
• HDAC1 protein, human
• Histone Deacetylase 1
• Histone Deacetylases

Topics

• Adult
• Aged
• Aged, 80 and over
• Female
• Histone Deacetylase 1
• Histone Deacetylases (metabolism)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Immunohistochemistry
• Male
• Middle Aged
• Pancreatic Neoplasms (metabolism, mortality, pathology, surgery)
• Prognosis
• Repressor Proteins (metabolism)
• Survival Rate
• Trans-Activators