دورية أكاديمية
Progesterone receptor-Grb2 interaction is associated with better outcomes in breast cancer.
| العنوان: | Progesterone receptor-Grb2 interaction is associated with better outcomes in breast cancer. |
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| المؤلفون: | Wittayavimol N; Department of Clinical Chemistry and Graduate Program in Clinical Biochemistry and Molecular Medicine, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand., Iwabuchi E; Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan., Pateetin P; Department of Clinical Chemistry and Graduate Program in Clinical Biochemistry and Molecular Medicine, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok 10330, Thailand., Miki Y; Department of Disaster Obstetrics and Gynecology, International Research Institute of Disaster Science (IRIDes), Tohoku University, Sendai, Japan., Onodera Y; Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan., Sasano H; Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan., Boonyaratanakornkit V; Excellence Center in Cancer and Inflammation, Chulalongkorn University, Bangkok, Thailand. Electronic address: Viroj.b@chula.ac.th. |
| المصدر: | The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2024 Mar; Vol. 237, pp. 106441. Date of Electronic Publication: 2023 Dec 08. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Pergamon Country of Publication: England NLM ID: 9015483 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-1220 (Electronic) Linking ISSN: 09600760 NLM ISO Abbreviation: J Steroid Biochem Mol Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Oxford ; New York : Pergamon, c1990- |
| مواضيع طبية MeSH: | Receptors, Progesterone*/genetics , Breast Neoplasms*/genetics, Humans ; Female ; Epidermal Growth Factor ; Progesterone ; Signal Transduction/physiology ; Protein Binding |
| مستخلص: | In addition to mediating nuclear transcription, PR mediates extranuclear functions mainly through the PR polyproline domain (PPD) interaction with the SH3 domain of cytoplasmic signaling molecules. PR-PPD-SH3 interaction inhibits EGF-mediated signaling and decreases lung cancer cell proliferation. Grb2 is an essential adaptor molecule with an SH2 domain flanked by two SH3 domains. In this study, we examined whether PR, through interaction between PR-PPD and Grb2-SH3, can interact with Grb2 in cells and breast cancer tissues. Our previous study shows that interaction between PR-PPD and Grb2 could interfere with cytoplasmic signaling and lead to inhibition of EGF-mediated signaling. GST-pulldown analysis shows that PR-PPD specifically interacts with the SH3 domains of Grb2. Immunofluorescence staining shows colocalization of PR and Grb2 in both the nucleus and cytoplasm in BT-474 breast cancer cells. Using Bimolecular Fluorescence Complementation (BiFC) analysis, we show that PR and Grb2 interact in breast cancer cells through the Grb2-SH3 domain. Proximity Ligation Assay (PLA) analysis of 43 breast cancer specimens shows that PR-Grb2 interaction is associated with low histological stage and negatively correlates with lymph node invasion and metastasis in breast cancer. These results, together with our previous findings, suggest that PR-PPD interaction with Grb2 plays an essential role in PR-mediated growth factor signaling inhibition and could contribute significantly to better prognosis in PR- and Grb2-positive breast cancer. Our finding provides a basis for additional studies to explore a novel therapeutic strategy for cancer treatment. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier Ltd. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Breast cancer; Grb2; Progesterone receptor; Protein-Protein interaction; SH3 domain |
| المشرفين على المادة: | 0 (Receptors, Progesterone) 62229-50-9 (Epidermal Growth Factor) 4G7DS2Q64Y (Progesterone) |
| تواريخ الأحداث: | Date Created: 20231209 Date Completed: 20240205 Latest Revision: 20240312 |
| رمز التحديث: | 20240312 |
| DOI: | 10.1016/j.jsbmb.2023.106441 |
| PMID: | 38070754 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-1220 |
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| DOI: | 10.1016/j.jsbmb.2023.106441 |