Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells / 浙江大学学报(英文版)(B辑:生物医学和生物技术)
Journal of Zhejiang University. Science. B
;
(12): 39-48, 2019.
Article
in English
| WPRIM
| ID: wpr-1010442
ABSTRACT
Interferon-γ (IFN-γ) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Signal Transduction
/
Cell Transformation, Neoplastic
/
Cells, Cultured
/
Proto-Oncogene Proteins c-abl
/
Valproic Acid
/
Interferon-gamma
/
Cell Cycle Proteins
/
Cell Proliferation
/
Epithelial Cells
/
Histone Deacetylase 2
Limits:
Animals
Language:
English
Journal:
Journal of Zhejiang University. Science. B
Year:
2019
Type:
Article
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