deltanp63alpha-mediated induction of epidermal growth factor receptor promotes pancreatic cancer cell growth and chemoresistancedeltanp63alpha-mediated诱导表皮生长因子受体促进胰腺癌细胞生长和药物抗性.pdfVIP

DeltaNp63alpha-Mediated Induction of Epidermal Growth Factor Receptor Promotes Pancreatic Cancer Cell Growth and Chemoresistance 1,2 3¤ 2 1 Alexey V. Danilov , Divas Neupane , Archana Sidalaghatta Nagaraja , Elena V. Feofanova , Leigh Ann 1 3 1,2,3 Humphries , James DiRenzo , Murray Korc * 1 Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States of America, 2 Norris Cotton Cancer Center, Dartmouth- Hitchcock Medical Center, Lebanon, New Hampshire, United States of America, 3 Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire, United States of America Abstract Pancreatic ductal adenocarcinoma (PDAC) is highly resistant to current chemotherapy regimens, in part due to alterations in the p53 tumor suppressor pathway. p53 homolog p63 is a transcription factor essential for the development and differentiation of epithelial surfaces. However its function in cancer is controversial and its role in PDAC is not known. We discovered that DNp63a was the predominantly expressed p63 variant in pancreatic cancer cell lines. DNp63a protein and mRNA levels were high in T3M4, BxPC3 and COLO-357 pancreatic cancer cells and low in ASPC-1 and PANC-1 cells. Overexpression of DNp63a in PANC-1 cells and shRNA-mediated knockdown in T3M4 cells indicated that DNp63a promoted anchorage-dependent and -independent growth, motility and invasion, and enhanced resistance to cisplatin-induced apoptosis. Epidermal growth factor receptor (EGFR) signaling pathways contribute to the biological aggressiveness o