The Polymorphism of Hypoxia-inducible Factor-1a Gene in Endometrial Cancer

Kafshdooz, Leila; Tabrizi, Ali Dastranj; Mohaddes, Seyyed Mojtaba; Kafshdooz, Taiebeh; Akbarzadeh, Abolfazl; Ghojazadeh, Morteza; Gharesouran, Jalal

doi:10.7314/apjcp.2014.15.23.10393

Cited by 10 publications

(6 citation statements)

References 26 publications

(28 reference statements)

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“…This finding can be explained by the fact that protein translation and proteasome-dependent degradation are impaired by hypoxia, which affects the HIF-1α levels (Anad et al, 2011). Furthermore, these results are in line with the previous findings indicating that mature and functional HIF-1α are generated by cells in response to hypoxia in solid tumors (Kafshdooz et al, 2014) which plays a pivotal role in tumor progression, infiltration and metastasis (Unwith et al, 2015). The results yielded by this study also demonstrated that serum HIF-1α was significantly correlated with ANGPTL4 serum and expression levels.…”

Section: Discussionsupporting

confidence: 92%

Significance of Tissue Expression and Serum Levels of Angiopoietin-like Protein 4 in Breast Cancer Progression: Link to NF-κB /P65 Activity and Pro-Inflammatory Cytokines

Shafik¹,

Mohamed²,

Bedder³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Background:The molecular mechanisms linking breast cancer progression and inflammation still remain obscure. The aim of the present study was to investigate the possible association of angiopoeitin like protein 4 (ANGPTL4) and its regulatory factor, hypoxia inducible factor-1 α (HIF-1α), with the inflammatory markers nuclear factor kappa B/p65 (NF-κB /P65) and interleukin-1 beta (IL-1β) in order to evaluate their role in inflammation associated breast cancer progression. Materials and Methods: Angiopoietin-like protein 4 (ANGPTL4) mRNA expressions were evaluated using quantitative real time PCR and its protein expression by immunohistochemistry. DNA binding activity of NF-κB /P65 was evaluated by transcription factor binding immunoassay. Serum levels of ANGPTL4, HIF-1α and IL-1β were immunoassayed. Tumor clinico-pathological features were investigated. Results: ANGPTL4 mRNA expressions and serum levels were significantly higher in high grade breast carcinoma (1.47±0.31 and 184.98±18.18, respectively) compared to low grade carcinoma (1.21±0.32 and 171.76±7.58, respectively) and controls (0.70±0.02 and 65.34±6.41, respectively), (p<0.05). Also, ANGPTL4 high/moderate protein expression was positively correlated with tumor clinico-pathological features. In addition, serum levels of HIF-1α and IL-1β as well as NF-κB /P65 DNA binding activity were significantly higher in high grade breast carcinoma (148.54±14.20, 0.79±0.03 and 247.13±44.35 respectively) than their values in low grade carcinoma ( 139.14±5.83, 0.34±0.02 and 184.23±37.75, respectively) and controls (33.95±3.11, 0.11±0.02 and 7.83±0.92, respectively), (p<0.001). Conclusion: ANGPTL4 high serum levels and tissue expressions in advanced grade breast cancer, in addition to its positive correlation with tumor clinico-pathological features and HIF-1α could highlight its role as one of the signaling factors involved in breast cancer progression. Moreover, novel correlations were found between ANGPTL4 and the inflammatory markers, IL-1β and NF-κB/p65, in breast cancer, which may emphasize the utility of these markers as potential tools for understanding interactions for axes of carcinogenesis and inflammation contributed for cancer progression. It is thus hoped that the findings reported here would assist in the development of new breast cancer management strategies that would promote patients' quality of life and ultimately improve clinical outcomes. However, large-scale studies are needed to verify these results.

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Section: Discussionsupporting

confidence: 92%

Significance of Tissue Expression and Serum Levels of Angiopoietin-like Protein 4 in Breast Cancer Progression: Link to NF-κB /P65 Activity and Pro-Inflammatory Cytokines

Shafik¹,

Mohamed²,

Bedder³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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“…When the rate of tumor cell proliferation surpasses that of apoptosis, hypoxic foci begin to arise in the center of the growing tumor [131]. Hypoxiarelated centers of necrosis are among the most important inducers of angiogenesis at relatively early stages of cancer development through the production of the hypoxiainducible factor-1α (HIF-1α) [132]. Hypoxia-induced angiogenesis of the tumor, due to an increased release of HIF-1α, leads to a significant overexpression of VEGF, which usually increases the average microvascular density in the tissue [131,133].…”

Section: Hypoxia-inducible Factor 1 Dependent Cytokinesmentioning

confidence: 99%

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

2020

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Background Tumor initiation and subsequent progression are usually long-term processes, spread over time and conditioned by diverse aspects. Many cancers develop on the basis of chronic inflammation; however, despite dozens of years of research, little is known about the factors triggering neoplastic transformation under these conditions. Molecular characterization of both pathogenetic states, i.e., similarities and differences between chronic inflammation and cancer, is also poorly defined. The secretory activity of tumor cells may change the immunophenotype of immune cells and modify the extracellular microenvironment, which allows the bypass of host defense mechanisms and seems to have diagnostic and prognostic value. The phenomenon of immunosuppression is also present during chronic inflammation, and the development of cancer, due to its duration, predisposes patients to the promotion of chronic inflammation. The aim of our work was to discuss the above issues based on the latest scientific insights. A theoretical mechanism of cancer immunosuppression is also proposed. Conclusions Development of solid tumors may occur both during acute and chronic phases of inflammation. Differences in the regulation of immune responses between precancerous states and the cancers resulting from them emphasize the importance of immunosuppressive factors in oncogenesis. Cancer cells may, through their secretory activity and extracellular transport mechanisms, enhance deterioration of the immune system which, in turn, may have prognostic implications.

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“…HIF-1a is an oxygen stress factor that is highly expressed in hypoxia cells and has been increasingly recognized as playing a broad and critical role in normal development, postnatal physiology, cancer, and many other diseases ( 18 - 20 ). HIF-1a may be associated with EC based on the C1772T polymorphism ( 21 ). Horrée’s results showed that HIF-1a was not a risking factor for EC, although this study still maintains that HIF-1a promotes EC growth ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of Tra2-beta1 on proliferation, apoptosis, and metastasis of hypoxic endometrial carcinoma cell and its correlation with clinicopathological features

Sun¹,

Paudel²,

Song³

et al. 2020

Transl Cancer Res TCR

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Background This study aims to examine the influence of human transformer-2-beta1 (Tra2-beta1) on endometrial carcinoma (EC) development. The effects of Tra2-beta1 on the proliferation, apoptosis, invasion, and cell cycle of EC cells were also investigated. Methods Functional in vitro experiments were performed on Tra2-beta1 knockdown cells and hypoxic model cells. Western blot was used to detect HIF-1a, vascular endothelial growth factor (VEGF), and Tra2-beta1 protein expression; CCK8 assay was used to detect cell proliferation; flow cytometry was used to detect apoptosis and cell cycle, and Transwell assay was used to detect cell invasion ability. Tumor specimens were collected from 128 consecutive patients to detect the expression of Tra2-beta1, and the relationship between and EC and Tra-beta1 were analyzed by clinical pathological data, which included lymph node metastasis, pathological types, histological grade, myometrial invasion, etc. Results Tra2-beta1 was highly expressed in EC and was associated with clinical pathological features. It was related to the prognosis, and was found to promote proliferation (F=48.3, P<0.001) and migration (P<0.05), and inhibit apoptosis (P<0.05). Statistical analyses revealed a positive correlation between Tra2-beta1 and HIF-1a (correlation coefficient =0.36, P<0.001) and VEGF protein (correlation coefficient =0.23, P=0.021). In the hypoxic cell group and the combined intervention group, cell proliferation after 72 h was 9,783±45.6 and 6,783±68.4 (P<0.001), while the number of invasive cells was 421±16.8 and 276±11.2 (P<0.001), respectively. The apoptosis rates were 0.45±0.03 and 1.28±0.16, respectively (P<0.05). Conclusions The present findings demonstrate that the development of EC is positively correlated with Tra2-beta1. Tra2-beta1 may reverse the effect of hypoxia on EC, and this may provide new insights into the occurrence and development of EC.

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The Polymorphism of Hypoxia-inducible Factor-1a Gene in Endometrial Cancer

Cited by 10 publications

References 26 publications

Significance of Tissue Expression and Serum Levels of Angiopoietin-like Protein 4 in Breast Cancer Progression: Link to NF-κB /P65 Activity and Pro-Inflammatory Cytokines

Significance of Tissue Expression and Serum Levels of Angiopoietin-like Protein 4 in Breast Cancer Progression: Link to NF-κB /P65 Activity and Pro-Inflammatory Cytokines

Modeling of the immune response in the pathogenesis of solid tumors and its prognostic significance

Effects of Tra2-beta1 on proliferation, apoptosis, and metastasis of hypoxic endometrial carcinoma cell and its correlation with clinicopathological features

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