MAML1 regulates cell viability via the NF-κB pathway in cervical cancer cell lines

摘要: The Notch signaling pathway plays important roles in tumorigenesis a context-dependent manner. In human cervical cancer, alterations have been reported, and both tumor-suppressing tumor-promoting of proposed; however, the precise molecular mechanisms governing these cancer remain controversial. MAML is transcriptional co-activator originally identified by its role signaling. Recent evidence suggests that it also other pathways, such as p53 β-catenin pathways. required for stable formation complexes at promoters target genes. Chromosomal translocations affecting shown to promote tumorigenesis. this study, we used truncated dominant-negative MAML1 (DN-MAML) investigate HPV-positive cell lines. Three lines (HeLa, SiHa CaSki) expressed all receptors genes Hes1 MAML1. Among 3 lines, constitutive appearance cleaved Notch1 was found only CaSki cells, which constitutively activated line. Gamma secretase inhibitor (GSI) treatment, suppresses receptor activation, completely abrogated form but had no effect on viability. Overexpression DN-MAML retroviral transduction cells resulted significant decreases mRNA levels effects MAML1, or HPV E6/E7. expression induced increased viability without any cycle progression proliferation. addition, clonogenic assay experiments revealed overexpression colony compared control vector. When status NF-κB investigated, overexpressing exhibited loss phospho-IκBα, decreased total IκBα nuclear localization p65, hyperactivated. Furthermore, level detected when expressed. DN-MAML-overexpressing were treated with GSI, significantly observed, indicating inhibition using GSI treatment negatively affects Taken together, targeting may present novel method cells.