Myoepithelium promotes EMT in glandular epithelium by secreting/stimulating the expression of TGFβ1 to drive invasion in ductal carcinoma in situ of breast
10.3781/j.issn.1000-7431.2024.2403-0112
- VernacularTitle:肌上皮通过分泌/刺激TGFβ1的表达促进腺上皮发生EMT进而参与乳腺导管原位癌浸润的发生
- Author:
Yang YANG
1
;
Yumian JIA
1
;
Jiazhen LI
1
;
Jin WANG
1
;
Fangfang LIU
1
;
Xiaojing GUO
1
Author Information
1. 天津医科大学肿瘤医院,国家恶性肿瘤临床医学研究中心,天津市恶性肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,乳腺癌防治教育部重点实验室,天津 300060
- Publication Type:Journal Article
- Keywords:
Ductal carcinoma in situ of breast;
Glandular-epithelium;
Myoepithelium;
Epithelial-mesenchymal transition
- From:
Tumor
2024;44(10):1003-1014
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the regulatory mechanism of myoepithelial cells on glandular epithelial cells during the invasive process of ductal carcinoma in situ of breast.Methods:A total of 157 patients with ductal carcinoma in situ of breast,treated at the Tianjin Medical University Cancer Hospital from May 2008 to July 2010,were randomly selected(including 63 high nuclear grade patients,51 middle nuclear grade patients,and 43 low nuclear grade patients).Immunohistochemical staining for epithelial-mesenchymal transition(EMT)-related markers(Snail and ZEB1)was performed on tumor tissue specimens from these patients to explore the correlation between tumor cell nuclear grade,EMT process,and expression status of myoepithelial cells.To further investigate the regulatory role of myoepithelial cells on glandular epithelial cells during the invasive process of ductal carcinoma in situ of breast,a co-culture model of human myoepithelial cell line Hs578Bst and adenomatous epithelial cell line MCF-7 was established using Transwell chambers.Experimental,blank control,positive control,and negative control groups were designed by combining co-cultured Hs578Bst and MCF-7 cells with exogenous TGFβ1 and TGFβ1 inhibitors.After 72 hours of culture,morphological changes,migration and proliferation capabilities of MCF-7,as well as the changes in protein and mRNA expression levels of EMT-related genes(Snail and ZEB1),were observed in each group.Results:Immunohistochemical staining results demonstrated a positive correlation between tumor nuclear atypia,EMT activation,and myoepithelial cell expression in ductal carcinoma in situ tissues.The model of ductal carcinoma in situ of breast demonstrated that myoepithelial cells Hs578Bst promoted morphological changes in glandular epithelial cells MCF-7 by stimulating TGFβ1 expression.Wound healing and cell proliferation assays revealed that myoepithelial cells Hs578Bst can enhance migration and proliferation of glandular epithelial cells MCF-7 via TGFβ1 activation.Western blot and real-time quantitative PCR confirmed that myoepithelial cells Hs578Bst can upregulate the protein and mRNA expression levels of EMT-related genes(Snail and ZEB1)in glandular epithelial cells MCF-7 by through TGFβ1 stimulation.Conclusion:Breast myoepithelial cells promote EMT in glandular epithelial cells by secreting/stimulating TGFβ1,thereby contributing to the occurrence of invasion in ductal carcinoma in situ of the breast.
