Open AccessMammaglobin 1 mediates progression of trastuzumab‐resistant breast cancer cells through regulation of cyclins and NF‐κB
Author(s) -
Kusumastuti Ratih,
Kumagai Yuji,
Ishihara Seiichiro,
Enomoto Atsushi,
Murakami Takashi,
Yasuda Motoaki,
Haga Hisashi
Publication year - 2022
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13468
Subject(s) - trastuzumab , cyclin d1 , downregulation and upregulation , cancer research , cyclin dependent kinase , breast cancer , cyclin , medicine , cancer , biology , cell cycle , biochemistry , gene
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.