https://scholars.lib.ntu.edu.tw/handle/123456789/470161
標題: | Fibrillin-1, a novel TGF-beta-induced factor, is preferentially expressed in metaplastic carcinoma with spindle sarcomatous metaplasia | 作者: | HUANG-CHUN LIEN Lee Y.-H. Juang Y.-L. Lu Y.-T. |
關鍵字: | breast; epithelial-mesenchymal transition; fibrillin-1; metaplastic carcinoma; TGF-β | 公開日期: | 2019 | 出版社: | Elsevier B.V. | 卷: | 51 | 期: | 4 | 起(迄)頁: | 375-383 | 來源出版物: | Pathology | 摘要: | TGF-β induces epithelial–mesenchymal transition (EMT), which is involved in tumour progression. This study aims to identify and characterise novel factors potentially related to TGF-β-mediated tumour aggression in breast cancer. We treated the human mammary epithelial cell line MCF10A with TGF-β and observed TGF-β-dependent upregulation of FBN1, involving demethylation of CpG sites, in MCF10A cells undergoing EMT. The biological importance of fibrillin-1, encoded by FBN1, was evaluated through immunohistochemistry on 225 breast cancer specimens of various subtypes. Fibrillin-1 expression was observed only in metaplastic carcinoma of the breast (MCB) (51.7%), and the expression was observed in spindle sarcomatous metaplasia (SSM), but not in other metaplasia, including matrix-producing, pleomorphic, and squamous metaplasia, and carcinomatous components of both MCB and non-MCB. Fibrillin-1 expression was also restricted to the SSM of non-mammary carcinosarcomas of various organs. Overall, fibrillin-1 expression was enriched in MCB and non-mammary carcinosarcoma with SSM (93.7% and 93.3%, respectively), but not in MCBs and non-mammary carcinosarcoma without SSM. FBN1 knockdown in MDA-MB-231 cells with high FBN1 expression did not compromise migration, invasion, and tumourigenesis, and did not alter the expression of other EMT-related markers. In conclusion, fibrillin-1 is a novel TGF-β-induced marker. Fibrillin-1 expression in SSM, but not in other metaplasia and carcinomatous components, in both MCBs and non-mammary carcinosarcomas, together with the inability of FBN1-knockdown to compromise migration and invasion, indicates that fibrillin-1 is a marker induced solely in spindle metaplasia during EMT and does not induce EMT nor lead to tumour aggressiveness. ? 2019 Royal College of Pathologists of Australasia |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85064426215&doi=10.1016%2fj.pathol.2019.02.001&partnerID=40&md5=74292412f7fb7a43ea60f0b7ff39287d https://scholars.lib.ntu.edu.tw/handle/123456789/470161 |
ISSN: | 0031-3025 | DOI: | 10.1016/j.pathol.2019.02.001 | SDG/關鍵字: | cdh2 protein; fibrillin 1; fn protein; mitogen activated protein kinase 1; mitogen activated protein kinase 3; protein; protein kinase B; snai1 protein; stress activated protein kinase; synaptophysin; transcription factor Slug; transcription factor ZEB1; Twist related protein 1; unclassified drug; uvomorulin; vim protein; vimentin; fibrillin 1; transforming growth factor beta; Article; breast carcinoma; breast epithelium cell; cancer growth; carcinogenesis; carcinosarcoma; cell invasion; cell migration; controlled study; DNA demethylation; down regulation; gene expression; gene knockdown; human; human cell; human tissue; immunofluorescence; immunohistochemistry; MCF-7 cell line; MDA-MB-231 cell line; MDA-MB-468 cell line; metaplastic carcinoma; microarray analysis; priority journal; promoter region; reverse transcription polymerase chain reaction; SK-BR-3 cell line; spindle sarcomatous metaplasia; squamous cell metaplasia; T-47D cell line; upregulation; breast; breast tumor; cell transformation; epithelial mesenchymal transition; epithelium cell; female; gene expression regulation; genetics; metabolism; metaplasia; pathology; sarcoma; tumor cell line; Breast; Breast Neoplasms; Carcinosarcoma; Cell Line, Tumor; Cell Transformation, Neoplastic; Epithelial Cells; Epithelial-Mesenchymal Transition; Female; Fibrillin-1; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Immunohistochemistry; Metaplasia; Sarcoma; Transforming Growth Factor beta; Up-Regulation |
顯示於: | 病理學科所 |
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