scholarly journals Gene signatures of cyclin-dependent kinases: a comparative study in naïve early and advanced stages of lung metastasis breast cancer among pre- and post-menopausal women

2021 ◽  
2019 ◽  
Vol 65 (6) ◽  
pp. 825-831
Author(s):  
Lyudmila Belskaya ◽  
Viktor Kosenok

Currently, the urgent task is to search for new biomarkers as a promising tool for early detection and monitoring of breast cancer. The aim of the study was to study the level of cytokines in the saliva of patients with breast cancer. In the case-control study volunteers participated, which were divided into 3 groups: the main (breast cancer, n = 43), the comparison group (fibroadenoma, n = 32) and the control group (conditionally healthy, n = 39). All participants were questioned; biochemical examination of saliva, histological verification of the diagnosis was carried out. Intergroup differences are estimated by a nonparametric criterion. It is shown that in the context of breast cancer, the level of cytokines (IL-2, IL-4, IL-6, IL-10 and IL-18) is increasing, except for IL-8, the content of which decreases compared to the control group. When the disease progresses by the nature of the dynamics, the parameters are divided into two groups: IL-2, IL-4, IL-18 and IL-6, IL-8, IL-10. For the first group of cytokines, there was a decrease in content during the transition from the early stages to the more common ones. For the second group, when passing from stages T1-2N0M0 to T1-2NjM0, the level of cytokines remains practically constant. In the future, the level of cytokines is observed for stage T3_4N0_2M0, and for IL-2, IL-4 and IL-10, the level of cytokines reaches values corresponding to early stages, whereas for IL-6, IL-8 and IL-18 in the same direction, a significant increase in indicators was noted. Additionally, the IL-6/IL-8 ratio was calculated depending on the tumor size, as well as the presence / absence of metastasis. It is shown that this ratio is statistically significantly increased in the advanced stages of the disease. Particularly interesting is the increase in this ratio in saliva at the initial stages of the disease.


2020 ◽  
Vol 20 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Fang Peng ◽  
Chuansheng Yang ◽  
Yanan Kong ◽  
Xiaojia Huang ◽  
Yanyu Chen ◽  
...  

Background: CDK12 is a promising therapeutic target in breast cancer with an effective ability of maintaining cancer cell stemness. Objective: We aim to investigate the mechanism of CDK12 in maintaining breast cancer stemness. Methods: CDK12 expression level was accessed by using RT-qPCR and IHC. CDK12-altered breast cancer cell lines MDA-MB-231-shCDK12 and SkBr-3-CDK12 were then established. CCK8, colony formation assays, and xenograft model were used to value the effect of CDK12 on tumorigenicity. Transwell assay, mammosphere formation, FACS, and lung metastasis model in vivo were determined. Western blot further characterized the mechanism of CDK12 in breast cancer stemness through the c-myc/β-catenin pathway. Results: Our results showed a higher level of CDK12 exhibited in breast cancer samples. Tumor formation, cancer cell mobility, spheroid forming, and the epithelial-mesenchymal transition will be enhanced in the CDK12high group. In addition, CDK12 was associated with lung metastasis and maintained breast cancer cell stemness. CDK12high cancer cells presented higher tumorigenicity and a population of CD44+ subset compared with CDK12low cells. Our study demonstrated c-myc positively expressed with CDK12. The c-myc/β-catenin signaling was activated by CDK12, which is a potential mechanism to initiate breast cancer stem cell renewal and may serve as a potential biomarker of breast cancer prognosis. Conclusion: CDK12 overexpression promotes breast cancer tumorigenesis and maintains the stemness of breast cancer by activating c-myc/β-catenin signaling. Inhibiting CDK12 expression may become a potential therapy for breast cancer.


Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3644
Author(s):  
Daeun You ◽  
Yisun Jeong ◽  
Sun Young Yoon ◽  
Sung A Kim ◽  
Eunji Lo ◽  
...  

Interleukin-1 (IL1) is a proinflammatory cytokine and promotes cancer cell proliferation and invasiveness in a diversity of cancers, such as breast and colon cancer. Here, we focused on the pharmacological effect of Entelon® (ETL) on the tumorigenesis of triple-negative breast cancer (TNBC) cells by IL1-alpha (IL1A). IL1A enhanced the cell growth and invasiveness of TNBC cells. We observed that abnormal IL1A induction is related with the poor prognosis of TNBC patients. IL1A also increased a variety of chemokines such as CCL2 and IL8. Interestingly, IL1A expression was reduced by the ETL treatment. Here, we found that ETL significantly decreased the MEK/ERK signaling pathway in TNBC cells. IL1A expression was reduced by UO126. Lastly, we studied the effect of ETL on the metastatic potential of TNBC cells. Our results showed that ETL significantly reduced the lung metastasis of TNBC cells. Our results showed that IL1A expression was regulated by the MEK/ERK- and PI3K/AKT-dependent pathway. Taken together, ETL inhibited the MEK/ERK and PI3K/AKT signaling pathway and suppressing the lung metastasis of TNBC cells through downregulation of IL1A. Therefore, we propose the possibility of ETL as an effective adjuvant for treating TNBC.


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