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TRIM39 is a poor prognostic factor for patients with estrogen receptor‐positive breast cancer and promotes cell cycle progression
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- Takuya Ogura
- Department of Systems Aging Science and Medicine Tokyo Metropolitan Institute of Gerontology Tokyo Japan
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- Kotaro Azuma
- Department of Systems Aging Science and Medicine Tokyo Metropolitan Institute of Gerontology Tokyo Japan
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- Toshihiko Takeiwa
- Department of Systems Aging Science and Medicine Tokyo Metropolitan Institute of Gerontology Tokyo Japan
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- Junichiro Sato
- Department of Pathology Toranomon Hospital Tokyo Japan
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- Keiichi Kinowaki
- Department of Pathology Toranomon Hospital Tokyo Japan
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- Kazuhiro Ikeda
- Division of Systems Medicine and Gene Therapy Saitama Medical University Saitama Japan
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- Hidetaka Kawabata
- Department of Breast and Endocrine Surgery Toranomon Hospital Tokyo Japan
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- Satoshi Inoue
- Department of Systems Aging Science and Medicine Tokyo Metropolitan Institute of Gerontology Tokyo Japan
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Description
<jats:title>Abstract</jats:title><jats:p>Tripartite motif (TRIM) family proteins are involved in various biological processes and the pathophysiology of cancers. However, the roles of TRIM39, a TRIM family member, in breast cancer is not well‐understood. Here, we performed immunohistochemical study of TRIM39 protein in clinical estrogen receptor‐positive (ER<jats:sup>+</jats:sup>) breast cancer tissues from 108 patients. TRIM39 immunoreactivity (IR) was positively correlated with advanced stage (<jats:italic>p</jats:italic> < 0.001), large invasive tumor size (<jats:italic>p</jats:italic> = 0.012), and positive lymph node status (<jats:italic>p</jats:italic> = 0.002). Positive TRIM39 IR was significantly correlated with short disease‐free survival (DFS) (<jats:italic>p</jats:italic> = 0.001). Multivariate analysis revealed that the TRIM39 status is an independent prognostic factor in DFS (<jats:italic>p</jats:italic> = 0.049). Microarray analysis of MCF‐7 breast cancer cells treated with siRNA revealed that TRIM39 knockdown downregulated the cell cycle‐ and cell division‐related genes, including <jats:italic>MLLT11</jats:italic>, <jats:italic>CDCA3</jats:italic>, <jats:italic>CDC25C</jats:italic>, <jats:italic>BIRC5</jats:italic>, and <jats:italic>ANP32E</jats:italic>. Consistently, TRIM39 knockdown significantly suppressed proliferation and cell cycle transition to S phase in MCF‐7 and 4‐hydroxytamoxifen‐resistant (OHTR) breast cancer cells. These results suggest that TRIM39 promotes ER<jats:sup>+</jats:sup> breast cancer growth by promoting cell cycle progression.</jats:p>
Journal
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- Pathology International
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Pathology International 72 (2), 96-106, 2021-12-08
Wiley
