Net Expression Inhibits the Growth of Pancreatic Ductal Adenocarcinoma Cell PL45 In Vitro and In Vivo

Abstract

Pancreatic ductal adenocarcinoma has a poor prognosis due to late diagnosis and a lack of effective therapeutic options. Thus, it is important to better understand its molecular mechanisms and to develop more effective treatments for the disease. The ternary complex factor Net, which exerts its strong inhibitory function on transcription of proto-oncogene gene c-fos by forming ternary complexes with a second transcription factor, has been suspected of being involved in pancreatic cancer and other tumors biology. In this study, we found that the majority of pancreatic ductal adenocarcinoma tissues and cell lines had weak or no expression of Net, whereas significantly high level of Net expression occurred in paired adjacent normal tissues we studied. Furthermore, using in vitro and in vivo model systems, we found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. Our data thus suggested that Net might play an important role in pancreatic carcinogenesis, possibly by acting as a tumor suppressor gene.

Silencing of ELK3 Induces S-M Phase Arrest and Apoptosis and Upregulates SERPINE1 Expression Reducing Migration in Prostate Cancer Cells

“…ELK3 belongs to the ETS oncogene family and plays an important role in many biological processes such as cell proliferation, migration, invasion, and angiogenesis [11][12][13][14], which has been proved to promote the progression of several types of tumors including breast cancer, liver cancer, and squamous cell carcinomas [11-13, 15, 31]. On the contrary, some researchers reported that ELK3 was less expressed in cervical cancer and pancreatic cancer, and its ectopic expression inhibited the growth of these cancer cells [32][33][34].…”

S100 family signaling network and related proteins in pancreatic cancer (Review)

“…p21/WAF1 is also known as cyclindependent kinase (CDK) inhibitor 1 or CDK-interacting protein 1. p21/WAF1 is a cell cycle checkpoint, where cells either set about repairing themselves or commit suicide through apoptosis (52,53). The p21/WAF1 protein functions as a regulator of cell cycle progression at the G1 phase by inhibiting cyclin-CDK2 or -CDK1 activity (52,54,55). The expression of its gene is tightly controlled by p53, through which the p21/WAF1 protein mediates p53-dependent cell cycle G1 phase arrest, in response to a variety of stress stimuli (24,55).…”

Expression of c-fos Was Associated with Clinicopathologic Characteristics and Prognosis in Pancreatic Cancer

“…Furthermore, the findings that c-fos was down-regulated in PC with lymph node metastasis and increased c-fos expression induced multidrug resistance 1 (MDR1) in PC cells indicate the complex roles of the molecule in PC [ 21 , 22 ]. Other investigations that showed that c-fos contributes to cell motility [ 30 ] and functions as one of targets of some tumor suppressor genes [ 31 , 32 ], support its oncogenic potential in PC. In the current investigation, expression of c-fos was first detected for more than 300 patients with PC.…”