Reduced expression of PHD2 prolyl hydroxylase gene in primary advanced uterine cervical carcinoma

Roszak, A.; Kędzia, Witold; Malkowska-Walczak, Blanka; Pawlik, P.; Kedzia, H; Łuczak, Michał W.; Lianeri, Margarita; Jagodzińśki, Paweł P.

doi:10.1016/j.biopha.2011.03.005

Cited by 7 publications

(9 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A direct, negative regulatory mechanism, which limits accumulation of HIF-1A in hypoxia through induction of PHDs, has been reported by several investigators (61)(62)(63)(64)(65)(66)(67). In our previously published report (38) we found significantly lower levels of PHD2 transcript and protein levels in cancerous tissue than in the corresponding normal tissue. We did not observe a negative feedback loop to limit HIF-1 via induction of PHDs.…”

Section: Normal Tissue Cancerous Tissue -----------------------------supporting

confidence: 40%

“…The inhibition of PHDs activity due to decreased oxygen levels is considered critical for HIF-1A escape from proteosome degradation during hypoxia because the affinity of VHL for the non-hydroxylated HIF-1A is much lower (35)(36)(37). Our previous research and that published by Roszak et al (38) show for the first time a full analysis of the hypoxia pathway in primary advanced uterine cervical carcinoma.…”

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

confidence: 54%

“…Similarly, correlation between low pO 2 and high immunohistochemically detected HIF-1A was also described in advanced head and neck cancer (48). Decreased pO 2 in cancerous tissue favors HIF-1A accumulation during hypoxia because PDH2 expression is depleted at low oxygen levels (38).…”

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

confidence: 77%

“…Therefore, mutations present in the promoter region of the PHD2 gene could perturb the negative feedback loop of the hypoxia pathway. We found single nucleotide mutations in the PHD2 promoter, which normally provides binding sites for transcription factors (38). These mutations may remove binding sites for transcription factors, which are required for hypoxia HIF-1A induced expression (69) of PHD2.…”

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

confidence: 92%

See 3 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Normal Tissue Cancerous Tissue -----------------------------supporting

confidence: 40%

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

confidence: 54%

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

confidence: 77%

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

confidence: 92%

See 2 more Smart Citations

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

Self Cite

View full text Add to dashboard Cite

show abstract

“…Усиление трансляции мРНК HIF-1a может быть результатом гиперактивированного состояния PI3K/Akt/mTOR-сигнального пути, свойственного многим типам рака, включая РШМ [66]. Становятся также известны ВПЧ-специфичные механизмы увеличения активности или количества HIF-1a [67,68]. Например, обнаружена способность белка Е7 непосредственно связываться с HIF-1a и вытеснять его из комплекса с гистондеацетилазами (HDAC1, HDAC4, HDAC7), стимулируя тем самым формирование активного транскрипционного комплекса [67].…”

Section: транскрипционные факторы: фактор индуцированный гипоксией-1unclassified

Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development

et al. 2015

BIOMED KHIM

View full text Add to dashboard Cite

Ability to stimulate angiogenesis/lymphangiogenesis is recognized as an inherent feature of cancer cells providing necessary conditions for their growth and dissemination. “Angiogenic switch” is one of the earliest consequences of malignant transformation that encompasses a great number of genes and triggers a complex set of signaling cascades in endothelial cells. The processes of tumor microvasculature development are closely connected to the steps of carcinogenesis (from benign lesions to invasive forms) and occur through multiple deviations from the norm. Analysis of expression of proangiogenic factors at successive steps of cervical cancer development (intraepithelial neoplasia, cancer in situ, microinvasive, and invasive cancer) enables to reconstruct the regulatory mechanisms of (lymph-)angiogenesis and to discriminate the most important components. This review presents detailed analysis of literature data on expression of the key regulators of angiogenesis in cervical intraepithelial neoplasia and cervical cancer. Their possible involvement in molecular mechanisms of neoplastic transformation of epithelial cells, as well as invasion and tumor metastasis is discussed. Correlation between expression of proangiogenic molecular factors and various clinicopathological parameters is considered, the potential of their use in molecular diagnostics and targeted therapy of cervical cancer is reviewed. Particular attention is paid to relatively poorly studied regulators of lymphangiogenesis and “non-VEGF dependent”, or alternative, angiogenic pathways that constitute the prospect of future research in the field.

show abstract

EGLN1: A Biomarker of Poor Prognosis of Cervical Cancer and a Target of Treatment

Zhang,

Xu,

2024

Genetic Testing and Molecular Biomarkers

View full text Add to dashboard Cite

Reduced expression of PHD2 prolyl hydroxylase gene in primary advanced uterine cervical carcinoma

Cited by 7 publications

References 40 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

Remodeling of angiogenesis and lymphangiogenesis in cervical cancer development

EGLN1: A Biomarker of Poor Prognosis of Cervical Cancer and a Target of Treatment

Contact Info

Product

Resources

About