Genistein Directly Represses the Phosphorylation of STAT5 in Lactating Mammary Epithelial Cells.

ACS Omega

Laboratory of Cell and Tissue Biology, Research Faculty of Agriculture, Hokkaido University, North 9, West 9 060-8589 Sapporo, Japan.

Published: September 2021

Genistein is a soy isoflavone and shows various physiological activities, such as affinities for estrogen receptors (ERs) and inhibitory effects on the epidermal growth factor receptor (EGFR) pathway. A previous study reported that genistein downregulates milk production ability in mammary epithelial cells (MECs) while decreasing the phosphorylation of STAT5. The ER and EGFR pathways indirectly regulate STAT5. In this study, the repressing mechanism of genistein against the phosphorylation of STAT5 was investigated using a culture model of mouse MECs with milk production ability. The results revealed that genistein did not influence the behavior of ERα and ERβ, whereas genistein immediately repressed the phosphorylation of ERK1/2. However, the decrease in phosphorylated STAT5 occurred independent of the phosphorylation of EGFR. Genistein repressed new phosphorylation of STAT5 by prolactin without influencing the phosphorylation of JAK2. In conclusion, this study indicates that genistein directly inhibits the phosphorylation of STAT5 in lactating MECs.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427774PMC
http://dx.doi.org/10.1021/acsomega.1c03107DOI Listing

Publication Analysis

Top Keywords

phosphorylation stat5
20
genistein
8
genistein directly
8
phosphorylation
8
stat5 lactating
8
mammary epithelial
8
epithelial cells
8
milk production
8
production ability
8
genistein repressed
8

Similar Publications

FLT3 mutations are among the most common genetic alterations in acute myeloid leukemia (AML) and are associated with poor prognosis. Significant advancements have been made in developing FLT3 inhibitors (FLT3Is), such as quizartinib, which have improved treatment outcomes in both newly diagnosed and relapsed/refractory AML. Resistance to FLT3Is remains a major clinical challenge, driven by diverse mechanisms including FLT3 point mutations, cellular escape pathways, and the influence of the bone marrow microenvironment.

View Article and Find Full Text PDF

FLT3 inhibitors induce p53 instability, driven by STAT5/MDM2/p53 competitive interactions in acute myeloid leukemia.

Cancer Lett

January 2025

Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, Guangdong, China. Electronic address:

Article Synopsis
  • FLT3 mutations are common in AML, making them a key target for therapy, but resistance to FLT3 inhibitors is a significant challenge.
  • Tyrosine kinase inhibitors (TKIs) promote p53 degradation in FLT3-ITD AML cells through mechanisms involving STAT5 and MDM2, disrupting p53's role as a tumor suppressor.
  • Using MDM2 inhibitors alongside TKIs can stabilize p53 levels, enhancing the effectiveness of treatments and suggesting a promising combination approach for AML therapy.
View Article and Find Full Text PDF

Nobiletin: a potential erythropoietin receptor activator protects renal cells against hypoxia.

Apoptosis

January 2025

Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China.

Tangerine peel is a traditional Chinese herb and has been widely applied in foods and medicine for its multiple pharmacological effects. Erythropoietin receptor (EPOR), a member of the cytokine receptor family, is widely expressed in multiple tissues in especial kidney and plays protective effects in adverse physiological and pathological conditions. We hypothesized that it might be EPOR agonists existing in Tangerine peel bring such renal benefits.

View Article and Find Full Text PDF

Novel antileukemic compound with sub-micromolar potency against STAT5 addicted myeloid leukemia cells.

Eur J Med Chem

December 2024

INSERM UMR 1100 CEPR, Research Center for Respiratory Diseases, Team 2 "Proteolytic Enzymes and Their Pharmacological Targeting in Lung Diseases", 10 Boulevard Tonnellé, 37032, Tours, France. Electronic address:

Signal Transdcer and Activator of Transcription 5A and 5B (STAT5A/5B) are key effectors of tyrosine kinase oncogenes in myeloid leukemias. It is now clearly evidenced that inhibition of STAT5A/5B not only blocks the growth and survival of myeloid leukemia cells but also overcomes the resistance of leukemic cells to chemotherapy. Previous screening experiments allowed us to identify 17f as a lead compound with promising antileukemic activity that blocks the phosphorylation and transcriptional activity of STAT5A/5B in myeloid leukemia cells addicted to these proteins.

View Article and Find Full Text PDF

[Synergistic Effect of IGF1-R Inhibitor AEW541 on Imatinib Inducing SUP-B15 Cell Death].

Zhongguo Shi Yan Xue Ye Xue Za Zhi

December 2024

Blood Diseases Institute, Xuzhou Medical University, Department of Hematology, The Affiliated Hospital of Xuzhou Medical University.

Objective: To explore whether Ph acute lymphoblastic leukemia (ALL) cell line SUP-B15 treated with imatinib occurs a tolerant status charactered by cell proliferation suppression but apoptotic resistance, then evaluate whether IGF1-R inhibitor AEW541 can break this tolerance, and further explain its mechanisms.

Methods: SUP-B15 cells were treated with different concentrations of imatinib or AEW541. Cell proliferation was assayed by Deep Blue, and apoptotic cells were determined by Annexin V/7-AAD staining.

View Article and Find Full Text PDF

Want 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!