Tumour growth and resistance to gemcitabine of pancreatic cancer cells are decreased by AP-2α overexpression

Abstract

BACKGROUND: Activator protein-2a (AP-2a) is a transcription factor that belongs to the family of AP-2 proteins that have essential roles in tumorigenesis. Indeed, AP-2a is considered as a tumour-suppressor gene in different tissues such as colonic, prostatic or breast epithelial cells. Moreover, AP-2a also participates in the control of colon and breast cancer cells sensitivity towards chemotherapeutic drugs. Despite its potential interest, very few data are available regarding the roles of AP-2a in pancreatic cancer. METHODS: We have developed a stable pancreatic CAPAN-1 cell line overexpressing AP-2a. Consequences of overexpression were studied in terms of in vivo cell growth, gene expression, migration capacity and chemosensitivity. RESULTS: In vivo tumour growth of CAPAN-1 cells overexpressing AP-2a was significantly decreased by comparison to control cells. An altered expression pattern of cell cycle-controlling factors (CDK-4, CDK-6, cyclin-G1, p27 kip1 and p57

MicroRNAs in the Myocyte Enhancer Factor 2 (MEF2)-regulated Gtl2-Dio3 Noncoding RNA Locus Promote Cardiomyocyte Proliferation by Targeting the Transcriptional Coactivator Cited2

“…Cited2 has also been shown to regulate the expression of the cell cycle inhibitor p57 in hematopoietic stem cells, and p57 levels are decreased in the Cited2 knockout mouse (20,21). Furthermore, TFAP2 overexpression results in increased p57 expression (55). Consistent with the findings above, we showed that depletion of Cited2 results in decreased p57 expression, leading to increased cell cycle activity and cardiomyocyte proliferation.…”

Galectin-3 regulates MUC1 and EGFR cellular distribution and EGFR downstream pathways in pancreatic cancer cells

“…Irrelevant rabbit or mouse IgG was used as a negative control. Western blotting was performed as described in Jonckheere et al (2009). The membrane was probed with an anti-phospho-EGFR, anti-EGFR or anti-MUC1 (m8) antibody.…”

Inhibition of Notch3 enhances sensitivity to gemcitabine in pancreatic cancer through an inactivation of PI3K/Akt-dependent pathway

“…Pancreatic cancer is a leading cause of cancer-related death in the world and is characterized by rapid disease progression, highly invasive tumor phenotype, and resistance to chemotherapy [1,2]. Despite significant advances in diagnosis, staging, and surgical management of the disease, overall 2 years survival in US, Europe, Australia is around 20%, and 50-70% of patients may survive 2 years if treated with chemotherapy and surgery [1,2].…”

“…Despite significant advances in diagnosis, staging, and surgical management of the disease, overall 2 years survival in US, Europe, Australia is around 20%, and 50-70% of patients may survive 2 years if treated with chemotherapy and surgery [1,2]. Chemotherapy is the primary treatment option for most patients with pancreatic cancer, but the standard agents, such as fluorouracils (5-FU), capecitabine, and gemcitabine have had limited impact on patient survival [1,2]. Thus, the search for more effective chemotherapeutic agents is still ongoing, and new regimens are under active investigation.…”