Breast cancer expressing the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) is known as triple-positive (TPBC). TPBC represents 9-11% of breast cancer cases worldwide and is a heterogeneous subtype. Notably, TPBC presents a therapeutic challenge due to the crosstalk between the hormonal (ER and PR) and HER2 pathways. Patients with TPBC are treated with trastuzumab (TTZ); however, several patients treated with TTZ tend to relapse. The present study aimed to investigate the effect of the PR on inhibitory effect of TTZ on cell viability. BT474 cells (a model of TPBC) and BT474 PR-silenced cells were treated with either TTZ, progesterone (Pg), the PR antagonist mifepristone (RU486) or estradiol (E2) alone or in combination for 144 h (6 days). Cell viability assays and western blotting were subsequently performed. The results showed that Pg and E2 interfered with the inhibitory effect of TTZ on cell viability and this effect was potentiated when both hormones were combined. Pg was revealed to act through the PR, mainly activating the PR isoform B (PR-B) and inducing the protein expression levels of CDK4 and cyclin D1; however, it did not reactivate the HER2/Akt pathway. By contrast, E2 was able to increase PR isoform A (PR-A) expression, which was inhibited by Pg. Notably, in most of the experiments, RU486 did not antagonize the effects of Pg. In conclusion, Pg and E2 may interfere with the inhibitory effect of TTZ on cell viability through PR-B activation and PR-A inactivation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10688505 | PMC |
| http://dx.doi.org/10.3892/ol.2023.14152 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dense stroma activates the TGF-β1/FBW7 axis to induce metabolic subtype switching in pancreatic cancer.
Int J Surg
January 2025
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases. Although several chemotherapy regimens have been developed over the past decades, few targeted therapies have shown a significant improvement in overall survival, partly due to the identification of PDAC as a single disease.
Methods: Combining metabolomic analysis and immunohistochemistry staining with Oil Red O staining, analysis for the oxygen consumption rate and extracellular acidification rate, we stratified pancreatic cancer cells into two subtypes.
HER2 regulates autophagy and promotes migration in gastric cancer cells through the cGAS-STING pathway.
Anticancer Drugs
January 2025
Department of General Surgery and Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center.
In gastric cancer, the relationship between human epidermal growth factor receptor 2 (HER2), the cyclic GMP-AMP synthase-stimulator of the interferon genes (cGAS-STING) pathway, and autophagy remains unclear. This study examines whether HER2 regulates autophagy in gastric cancer cells via the cGAS-STING signaling pathway, influencing key processes such as cell proliferation and migration. Understanding this relationship could uncover new molecular targets for diagnosis and treatment.
View Article and Find Full Text PDFReceptor CDCP1 is a potential target for personalized imaging and treatment of poor outcome HER2+, triple negative and metastatic ER+/HER2- breast cancers.
Clin Cancer Res
January 2025
Mater Research Institute - University of Queensland, Woolloongabba, Qld, Australia.
Purpose: Receptor CUB-domain containing- protein 1 (CDCP1) was evaluated as a target for detection and treatment of breast cancer.
Experimental Design: CDCP1 expression was assessed immunohistochemically in tumors from 423 patients (119 triple-negative breast cancer (TNBC); 75 HER2+; 229 ER+/HER2- including 228 primary tumors, 229 lymph node and 47 distant metastases). Cell cytotoxicity induced in vitro by a CDCP1-targeting antibody-drug conjugate (ADC), consisting of the human/mouse chimeric antibody ch10D7 and the microtubule disruptor monomethyl auristatin E (MMAE), was quantified, including in combination with HER2-targeting ADC T-DM1.
To describe the subsets of malignant epithelial cells in gastric cancer, their developmental trajectories and drug resistance characteristics.
Discov Oncol
January 2025
West China School of Medicine, Sichuan University, Chengdu, China.
Gastric cancer is an aggressive malignancy characterized by significant clinical heterogeneity arising from complex genetic and environmental interactions. This study employed single-cell RNA sequencing, using the 10 × Genomics platform, to analyze 262,532 cells from gastric cancer samples, identifying 32 distinct clusters and 10 major cell types, including immune cells (e.g.
View Article and Find Full Text PDFAURKB affects the proliferation of clear cell renal cell carcinoma by regulating fatty acid metabolism.
Discov Oncol
January 2025
Department of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi, 710068, China.
Background: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer with a high metastatic rate and high mortality rate. The molecular mechanism of ccRCC development, however, needs further study. Aurora kinase B (AURKB) functions as an important oncogene in various tumors; therefore, in the present study, we aimed to explore the mechanism by which AURKB affects ccRCC development.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!