Expression of hypoxia-inducible factor-1alpha, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma: correlation with poor prognosis with possible regulation.
OBJECTIVE
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.
Miyake
Kotaro
K
Department of Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. kota166@clin.med.tokushima-u.ac.jp
Yoshizumi
Tomoharu
T
Imura
Satoru
S
Sugimoto
Koji
K
Batmunkh
Erdenebulgan
E
Kanemura
Hirofumi
H
Morine
Yuji
Y
Shimada
Mitsuo
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D012097:Repressor Proteins / Q000378:metabolism*; D015996:Survival Rate; D015534:Trans-Activators
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C089320:MTA1 protein, human; D012097:Repressor Proteins; D015534:Trans-Activators; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases