Mammaglobin 1 mediates progression of trastuzumab‐resistant breast cancer cells through regulation of cyclins and NF‐κB. Issue 10 (9th August 2022)

• Record Type: Journal Article
• Authors: Kusumastuti, Ratih; Kumagai, Yuji; Ishihara, Seiichiro; Enomoto, Atsushi; Murakami, Takashi; Yasuda, Motoaki; Haga, Hisashi
• Is Part Of: FEBS open bio. Volume 12:Issue 10(2022)
• Page Start: 1797
• Page End: 1813
• Publication Date: 2022-08-09
• Subjects: cyclin -- invasion -- MGB1 -- migration -- resistance -- trastuzumab; Molecular biology -- Periodicals; Cytology -- Periodicals; Life sciences -- Periodicals; Biological Science Disciplines -- Periodicals; Molecular Biology -- Periodicals; Cell Biology -- Periodicals; Cytology; Life sciences; Molecular biology; Periodicals; 572.805
• DOI: 10.1002/2211-5463.13468
• Languages: English
• ISSNs: 2211-5463

Abstract

Abstract : Overexpression of human epidermal growth factor receptor 2 (HER2) in various cancers is correlated with poor patient survival. Trastuzumab, a recombinant humanized monoclonal antibody against HER2, has been considered to be a first‐line therapy for HER2‐positive breast cancer patients, but its usefulness is limited by the development of resistance. In this study, we established resistant cells by long‐term treatment with trastuzumab. These cells showed higher proliferation, invasion, and migration abilities than the wild‐type cells. Mammaglobin 1 (MGB1), cyclin D1, E1, A2, and phosphorylated NF‐κB (p‐p65) were upregulated in resistant cells. These proteins regulate cell proliferation, migration, and invasion of resistant cells. Depletion of MGB1 decreased cyclin and p‐p65 expression. Cyclin D1 and A2, but not E1 expression, were affected by p‐p65 downregulation. In summary, our results indicate that MGB1 expression is increased in breast cancer cells that have gained resistance to trastuzumab, and suggest that MGB1 promotes aggressiveness through cyclin and NF‐κB regulation. Abstract : Trastuzumab is a first‐line therapy for HER2‐positive breast cancer patients, but its efficacy is limited by resistance. Our study revealed that resistant cells showed higher proliferation, invasion, and migration abilities than wild‐type cells. Mammaglobin 1 (MGB1) expression is increased in breast cancer cells that have gained resistance to trastuzumab, and MGB1 promotes aggressiveness through cyclin and NF‐κB regulation.