Natural HPV58 E6 and E7 Variants Detected in Thai Breast Cancer Patients Cooperate to Induce Loss of p53 and Increase Cell Growth

2021 ◽  
Vol 104 (6) ◽  
pp. 902-910
Keyword(s):  
Breast Cancer ◽  
Cervical Cancer ◽  
Cell Proliferation ◽  
Human Papillomavirus ◽  
Cell Growth ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Breast And Cervical Cancer ◽  
Cervical Cancer Cells ◽  
Hpv Oncoproteins

Background: Detection of human papillomavirus (HPV) in breast cancer patients has suggested a possible contributing role of the virus in cancer progression in this population. Objective: To investigate the presence of HPVs in Thai breast cancer patients and examine the potential activities of HPVs identified in both breast and cervical cancer cells. Materials and Methods: Fifty-five breast cancer tissues from Thai patients were subjected to HPV detection using PCR-EIA and DNA sequencing. Detection of HPV E6 proteins in sample tissues was examined by fluorescence immunohistochemistry. Cervical and two types of breast cancer cell lines expressing HPV oncogenes were established. The separate and combination of HPV oncoproteins activity for p53 degradation and specific gene regulation were investigated using western blot analysis and qPCR. Cell proliferation was assessed by MTT assay. Results: Twenty-two percent (10/45) of invasive breast cancers were found infected with various high-risk HPV types, with HPV58 E6D4G/E7T20IG63S being the most common variant. The percentage of HPV58 alone was approximately 50% (5/10) of all HPV positive samples. Similar potential oncogenic activity for this variant was observed in breast and cervical cancer cells. A separate analysis of single or combination of 58E6 (prototype or E6D4G) with 58E7 (prototype or E7T20IG63S) demonstrated that co-expression of 58E7T20IG63S with 58E6 (either prototype or E6D4G) significantly promoted cell proliferation compared to prototype 58E6/E7. Enhanced proliferation was mediated through elevated p53 degradation and reduced p21 expression. While p53 degradation activity was greatly diminished from E6 with D4G mutation, co-expression with E7T20IG63S cooperated to enhance degradation of p53 and promoted cell growth. Conclusion: HPV58 E6D4G/E7T20IG63S was the most HPV oncogene variant detected in Thai breast cancer patients. This variant exhibited in promoting cell proliferation and p53 degradation. A cooperative effect was observed in combination of HPV oncoproteins. Keywords: Human papillomavirus type 58; oncogene variant; breast cancer; Thai patients; altered cell growth

Genome-Wide Methylation Analysis Identifies NOX4 and KDM5A as Key Regulators in Inhibiting Breast Cancer Cell Proliferation by Ginsenoside Rg3

2018 ◽  
Vol 46 (06) ◽  
pp. 1333-1355 ◽  
Author(s):  
Juyeon Ham ◽  
Seungyeon Lee ◽  
Hyunkyung Lee ◽  
Dawoon Jeong ◽  
Sungbin Park ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Growth Effect ◽  
Breast Cancer Patients ◽  
Ginsenoside Rg3 ◽  
Methylation Analysis ◽  
Genome Wide

Ginsenoside Rg3 is a key metabolite of ginseng and is known to inhibit cancer cell growth. However, the epigenetics of CpG methylation and its regulatory mechanism have yet to be determined. Genome-wide methylation analysis of MCF-7 breast cancer cells treated with Rg3 was performed to identify epigenetically regulated genes and pathways. The effect of Rg3 on apoptosis and cell proliferation was examined by a colony formation assay and a dye-based cell proliferation assay. The association between methylation and gene expression was monitored by RT-PCR and Western blot analysis. Genome-wide methylation analysis identified the “cell morphology”-related pathway as the top network. Rg3 induced late stage apoptosis but inhibited cell proliferation up to 60%. Hypermethylated TRMT1L, PSMC6 and NOX4 were downregulated by Rg3, while hypomethylated ST3GAL4, RNLS and KDM5A were upregulated. In accordance, downregulation of NOX4 by siRNA abrogated the cell growth effect of Rg3, while the effect was opposite for KDM5A. Notably, breast cancer patients with a higher expression of NOX4 and KDM5A showed poor and good prognosis of survival, respectively. In conclusion, Rg3 deregulated tumor-related genes through alteration of the epigenetic methylation level leading to growth inhibition of cancer cells.

scholarly journals USP1 Regulates TAZ Protein Stability Through Ubiquitin Modifications in Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3090
Author(s):  
Ashley Mussell ◽  
He Shen ◽  
Yanmin Chen ◽  
Michalis Mastri ◽  
Kevin H. Eng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Protein Stability ◽  
Cancer Patients ◽  
Effector Proteins ◽  
Therapeutic Interventions ◽  
Hippo Signaling ◽  
Strong Positive Correlation ◽  
Breast Cancer Patients ◽  
Loss Of Function

The Hippo signaling pathway is an evolutionarily conserved pathway that was initially discovered in Drosophila melanogaster and was later found to have mammalian orthologues. The key effector proteins in this pathway, YAP/TAZ, are often dysregulated in cancer, leading to a high degree of cell proliferation, migration, metastasis and cancer stem cell populations. Due to these malignant phenotypes it is important to understand the regulation of YAP/TAZ at the protein level. Using an siRNA library screen of deubiquitinating enzymes (DUBs), we identified ubiquitin specific peptidase 1 (USP1) as a novel TAZ (WWTR1) regulator. We demonstrated that USP1 interacts with TAZ and increases TAZ protein stability. Conversely, loss of function of USP1 reduces TAZ protein levels through increased poly-ubiquitination, causing a decrease in cell proliferation and migration of breast cancer cells. Moreover, we showed a strong positive correlation between USP1 and TAZ in breast cancer patients. Our findings facilitate the attainment of better understanding of the crosstalk between these pathways and may lead to potential therapeutic interventions for breast cancer patients.

Prognostic value of vascular density and cell proliferation in breast cancer patients

1999 ◽  
Vol 195 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Olli Tynninen ◽  
Kristina von Boguslawski ◽  
Hannu J. Aronen ◽  
Timo Paavonen
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Vascular Density ◽  
Breast Cancer Patients

scholarly journals Exploration of Binding Interaction of Steroidal Drugs with HMG-CoA Reductase for the Treatment of Breast Cancer Patients who suffer with Cardiovascular Problems: In-silico Studies

2020 ◽  
Vol 5 (1) ◽  
pp. 27-33
Author(s):  
Varish Ahmad
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Patients ◽  
Cholesterol Synthesis ◽  
Breast Cancer Patients ◽  
Binding Interaction ◽  
Hmg Coa Reductase ◽  
Study Results ◽  
In Silico Studies ◽  
Coa Reductase

Introduction: HMG-CoA reductase is widely used as a significant target to screen cardiovascular therapeutics molecules because of its involvement in cholesterol synthesis and cell proliferation. Steroidal drugs like anastrozole, exemestane, letrozole have been tested as potential inhibitors of cancer mediated aromatase enzyme and these could be inhibited to HMG-CoA reductase so that the link with cholesterol synthesis and cell proliferation can be utilized to control cancers in. Objective: To test the binding affinity and binding patterns using computational methods of these drugs and established them as a HMG-CoA reductase inhibitor due to the involvement of this enzyme with cholesterol synthesis and cell proliferation can be utilized to control the cancers. Materials and methods: Freely available docking tools like AutoDock and web resources like DrugBank and PDB were used to extract data and conduct the study. Results: The binding interaction of exemestane has shown significant docking interactions which are followed by anastrozole and letrozole. Exemestane has shown binding energy -8.74 kcal/mol, hydrogen bond length: 1.97513 Å, and interacting amino acid was analyzed as A: ASN658:HD21-: UNK1: O6. The positive control statin was used in this study has shown significant binding interaction but it was less than tested exemestane.Conclusion: Thus, exemestane can potentially inhibit to HMG-CoA reductase enzyme even stronger than the clinically tested drug statin and would be a good choice for cancer patients. Thus, in vitro laboratory experimentation and in vivo research are necessary to put forward therapeutic repositioning of these drugs so they could be established as a broad spectrum potential anticancer drugs including breast cancer especially for the patient with cardiovascular complications.  

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