Important roles of estrogen receptor alpha in tumor progression and anti-estrogen therapy of pancreatic ductal adenocarcinoma

Xue, Jing; Yao, Ye; Yao, Qingyu; Tian, Xiuyun; Yu, Feng; Hong, Soon-Kwang; Kong, Daming; Cui, Can; Yan, Liang; Hao, Chunyi; Zhou, Tianyan

doi:10.1016/j.lfs.2020.118302

Cited by 8 publications

(5 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although ERα and ERβ were well-characterized ER isoforms, the results in literature findings of their expression on pancreatic cancer cell lines were conflicting [ 25 , 26 , 27 ]. According to our experimental results, all three cell lines expressed the ERα to a varying degree in nuclear localization ( Figure 7 A–C).…”

Section: Resultsmentioning

confidence: 99%

Investigation of the Antitumor Effects of Tamoxifen and Its Ferrocene-Linked Derivatives on Pancreatic and Breast Cancer Cell Lines

et al. 2022

View full text Add to dashboard Cite

Tamoxifen is a long-known anti-tumor drug, which is the gold standard therapy in estrogen receptor (ER) positive breast cancer patients. According to previous studies, the conjugation of the original tamoxifen molecule with different functional groups can significantly improve its antitumor effect. The purpose of this research was to uncover the molecular mechanisms behind the cytotoxicity of different ferrocene-linked tamoxifen derivates. Tamoxifen and its ferrocene-linked derivatives, T5 and T15 were tested in PANC1, MCF7, and MDA-MB-231 cells, where the incorporation of the ferrocene group improved the cytotoxicity on all cell lines. PANC1, MCF7, and MDA-MB-231 express ERα and GPER1 (G-protein coupled ER 1). However, ERβ is only expressed by MCF7 and MDA-MB-231 cells. Tamoxifen is a known agonist of GPER1, a receptor that can promote tumor progression. Analysis of the protein expression profile showed that while being cytotoxic, tamoxifen elevated the levels of different tumor growth-promoting factors (e.g., Bcl-XL, Survivin, EGFR, Cathepsins, chemokines). On the other hand, the ferrocene-linked derivates were able to lower these proteins. Further analysis showed that the ferrocene-linked derivatives significantly elevated the cellular oxidative stress compared to tamoxifen treatment. In conclusion, we were able to find two molecules possessing better cytotoxicity compared to their unmodified parent molecule while also being able to counter the negative effects of the presence of the GPER1 through the ER-independent mechanism of oxidative stress induction.

show abstract

Section: Resultsmentioning

confidence: 99%

Investigation of the Antitumor Effects of Tamoxifen and Its Ferrocene-Linked Derivatives on Pancreatic and Breast Cancer Cell Lines

et al. 2022

View full text Add to dashboard Cite

show abstract

“…ERbeta/ERalpha ratio may even affect the estrogen-mediated growth stimulation and then reduce cytotoxicity at physiological concentrations that may possess some clinical implications for pancreatic cancer therapy [ 40 ]. A recent study demonstrated the critical roles of estrogen receptors and the efficacies of anti-estrogen therapy in both pancreatic cancer cell’s proliferation as well as cancer progression’s inhibition [ 41 ]. In some previous studies, it was suggested that T-box factors, especially Tbx2, as transcription factors, play important roles in controlling cell cycle progression, embryonic development, and cancer genesis.…”

Section: Discussionmentioning

confidence: 99%

Novel insight into pancreatic adenocarcinoma pathogenesis using liquid association analysis

et al. 2022

View full text Add to dashboard Cite

Background Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy associated with a poor prognosis. High-throughput disease-related-gene expression data provide valuable information on gene interaction, which consequently lead to deeper insight about pathogenesis. The co-expression analysis is a common approach that is used to investigate gene interaction. However, such an approach solely is inadequate to reveal the complexity of the gene interaction. The three-way interaction model is known as a novel approach applied to decode the complex relationship between genes. Methods In the current study, the liquid association method was used to capture the statistically significant triplets involved in the PDAC pathogenesis. Subsequently, gene set enrichment and gene regulatory network analyses were performed to trace the biological relevance of the statistically significant triplets. Results The results of the current study suggest that “response to estradiol” and “Regulation of T-cell proliferation” are two critical biological processes that may be associated with the PDAC pathogenesis. Additionally, we introduced six switch genes, namely Lamc2, Klk1, Nqo1, Aox1, Tspan1, and Cxcl12, which might be involved in PDAC triggering. Conclusion In the current study, for the first time, the critical genes and pathways involved in the PDAC pathogenesis were investigated using the three-way interaction approach. As a result, two critical biological processes, as well as six potential biomarkers, were suggested that might be involved in the PDAC triggering. Surprisingly, strong evidence for the biological relevance of our results can be found in the literature.

show abstract

“…In our study, the AMRs of ovarian cancer, leukemia, prostate, lip/oral/pharyngeal, pancreatic, and breast cancers increased significantly beyond the predicted rates, especially in 2022. All of these cancers are known as estrogen and estrogen receptor alpha (ERα)-sensitive cancers [78][79][80][81][82][83]. Recent research by Solis et al on the binding ability of S-protein of SARS-CoV-2 against over 9,000 human proteins has shown that S-protein specifically binds to ERα and upregulates the transcriptional activity of ERα.…”

Section: Cancer Development By Sars-cov-2 Mrna Vaccinementioning

confidence: 99%

Increased Age-Adjusted Cancer Mortality After the Third mRNA-Lipid Nanoparticle Vaccine Dose During the COVID-19 Pandemic in Japan

Gibo,

Kojima,

Fujisawa

et al. 2024

Cureus

View full text Add to dashboard Cite

During the COVID-19 pandemic, excess deaths including cancer have become a concern in Japan, which has a rapidly aging population. Thus, this study aimed to evaluate how age-adjusted mortality rates (AMRs) for different types of cancer in Japan changed during the COVID-19 pandemic (2020-2022). Official statistics from Japan were used to compare observed annual and monthly AMRs with predicted rates based on pre-pandemic (2010-2019) figures using logistic regression analysis. No significant excess mortality was observed during the first year of the pandemic (2020). However, some excess cancer mortalities were observed in 2021 after mass vaccination with the first and second vaccine doses, and significant excess mortalities were observed for all cancers and some specific types of cancer (including ovarian cancer, leukemia, prostate cancer, lip/oral/pharyngeal cancer, pancreatic cancer, and breast cancer) after mass vaccination with the third dose in 2022. AMRs for the four cancers with the most deaths (lung, colorectal, stomach, and liver) showed a decreasing trend until the first year of the pandemic in 2020, but the rate of decrease slowed in 2021 and 2022. This study discusses possible explanations for these increases in age-adjusted cancer mortality rates.

show abstract

Important roles of estrogen receptor alpha in tumor progression and anti-estrogen therapy of pancreatic ductal adenocarcinoma

Cited by 8 publications

References 50 publications

Investigation of the Antitumor Effects of Tamoxifen and Its Ferrocene-Linked Derivatives on Pancreatic and Breast Cancer Cell Lines

Investigation of the Antitumor Effects of Tamoxifen and Its Ferrocene-Linked Derivatives on Pancreatic and Breast Cancer Cell Lines

Novel insight into pancreatic adenocarcinoma pathogenesis using liquid association analysis

Increased Age-Adjusted Cancer Mortality After the Third mRNA-Lipid Nanoparticle Vaccine Dose During the COVID-19 Pandemic in Japan

Contact Info

Product

Resources

About