Expression of hypoxia-inducible factor-1 alpha (HIF-1α) in patients with the gallbladder carcinoma

Batmunkh, Erdenebulgan; Shimada, Mitsuo; Morine, Yuji; Imura, Satoru; Kanemura, Hirofumi; Arakawa, Yusuke; Hanaoka, Jun; Kanamoto, Mami; Sugimoto, Koji; Nishi, Masaaki

doi:10.1007/s10147-009-0011-7

Cited by 29 publications

(24 citation statements)

References 30 publications

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“…Increased vascularity is observed in low grade cervical cancer, while this is usually a late event in the progression of many other cancers (20,22). Tissue hypoxia is a common feature of most solid tumors (15,23,24), often with heterogeneous O 2 levels within different regions of the individual tumors. The cellular adaptation to hypoxic The target mRNA levels were corrected to the amount of PBGD cDNA and expressed as multiplicity of these cDNA copies in the calibrator.…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of HIF-1A was described in many solid tumors such as gastric (23), gallbladder (24), colon, breast, lung, skin, ovarian, pancreatic, prostate and renal carcinoma (15). High expression of HIF-1A was also reported in cervical cancer tissue samples (21,(39)(40)(41)(42)(43)(44)(45)(46)(47), but only using the immunohistochemical method.…”

Section: Normal Tissue Cancerous Tissue -----------------------------mentioning

confidence: 99%

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Increased expression of HIF-1A and its implication in the hypoxia pathway in primary advanced uterine cervical carcinoma

Łuczak

Roszak²,

Pawlik³

et al. 2011

Oncol Rep

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Abstract. The development of cervical cancer exhibits some unique differences compared to other solid tumors. Normal cervical stratified epithelia have characteristics of hypoxic tissue. Lack of oxygen (hypoxia) induces the HIF-1 (hypoxiainducible factor-1) transcription factor, which is a heterodimer composed of a constitutively expressed β subunit and a hypoxia-inducible α-subunit. HIF-1A targets the transcription of over 70 genes involved in many aspects of cancer biology. In well-oxygenated environments, the HIF-1A subunit is hydroxylated, recognized and marked for proteosomal destruction by an E3 ubiquitin ligase, the von Hippel-Lindau protein (pVHL) complex. Under hypoxic stress, proline hydroxylase (PHD) activity is diminished, and stabilized HIF-1A is involved in the activation of the tissue response to hypoxia. Here, we examined the HIF-1A and VHL transcript levels and HIF-1A protein levels in cancerous tissue (n=30) and non-cancerous, normal uterine cervical tissue (n=30). We also compared the methylation status of HIF-1A and of the VHL promoter regions in cancerous and normal tissue samples. Significantly higher levels of HIF-1A and VHL transcripts (p<0.0001 and p= 0.0042, respectively) and of HIF-1A protein (p= 0.0037) were detected in cancerous tissue compared to normal samples. We did not observe DNA methylation in the HIF-1A and VHL promoter region in either control or cancerous tissue samples. VHL has a functional hypoxia response element (HRE) in the promoter region, and the induction of this HRE acts within a negative feedback loop to limit the hypoxic HIF-1A response. Our findings may suggest that HIF-1A could promote its own degradation by the induction of VHL gene expression (Spearman correlation coefficient, 0.515; p=0.003). Our study shows for the first time that this increase in VHL expression could be HIF-1A-dependent and serves within a negative feedback pathway during hypoxia to regulate the cell-specific oxygen threshold for HIF-1A activation.

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Section: Discussionmentioning

confidence: 99%

Section: Normal Tissue Cancerous Tissue -----------------------------mentioning

confidence: 99%

Increased expression of HIF-1A and its implication in the hypoxia pathway in primary advanced uterine cervical carcinoma

Łuczak

Roszak²,

Pawlik³

et al. 2011

Oncol Rep

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“…The detailed method was described elsewhere [24]. Briefly, 4-lm-thick sections were cut from archival formalin-fixed paraffin-embedded tissue blocks.…”

Section: Hif-1amentioning

confidence: 99%

CD133 expression is a potential prognostic indicator in intrahepatic cholangiocarcinoma

et al. 2010

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“…The stabilized α unit binds with its counterpart, the β subunit to form the activated HIF1 which is translocated to the nucleus to bind with the hypoxia-response element of the target gene promoter and enhances the transcription [4,5]. HIF-1α has been known to regulate the expression of a multitude of genes that are critically involved in tumor growth, angiogenesis, metastasis, venous invasion and chemoresistance [6,7]. A poor prognosis of GBC has also been associated with tumor neovascularisation promoted by the HIF-1α over expression [7].…”

Section: Introductionmentioning

confidence: 99%

Hispidulin inhibits proliferation and enhances chemosensitivity of gallbladder cancer cells by targeting HIF-1α

Gao

Xie

Peng

et al. 2015

Experimental Cell Research

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Expression of hypoxia-inducible factor-1 alpha (HIF-1α) in patients with the gallbladder carcinoma

Abstract: Expression of HIF-1alpha was correlated with the poor prognostic indicators, such as lymph node metastasis and venous invasion. Therefore, HIF-1alpha could serve as an auxiliary parameter for predicting malignant behavior for gallbladder carcinomas.

Cited by 29 publications

References 30 publications

Increased expression of HIF-1A and its implication in the hypoxia pathway in primary advanced uterine cervical carcinoma

Increased expression of HIF-1A and its implication in the hypoxia pathway in primary advanced uterine cervical carcinoma

CD133 expression is a potential prognostic indicator in intrahepatic cholangiocarcinoma

Hispidulin inhibits proliferation and enhances chemosensitivity of gallbladder cancer cells by targeting HIF-1α

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