Growth Inhibitory Effect of the Ternary Complex Factor Net on Human Pancreatic Carcinoma Cell Lines

Abstract

Pancreatic carcinoma is one of the most aggressive malignancies and carries the most dismal prognoses of all cancers. A better understanding of the genes involving in tumor development may allow us to tackle this rapidly progressive disease. The Net gene belongs to the ternary complex transcription factor (TCF) family and is regulated by the Ras/mitogen-activited protein kinase-signaling pathway. Under basal conditions, Net shows strong represssing function on transcription of proto-oncogene gene c-fos. Moreover, the lower expression of Net has been noted in some carcinoma cells, such as cervical cancer. To study the effect of Net on c-fos expression and its potential role in the growth of pancreatic carcinoma, we developed a recombinant plasmid, a pEGFP-N1-Net, which codes for Net-EGFP fusion proteins, and stably transfected it into BxPC-3 human pancreatic carcinoma cells. Using stable transformants, we were able to show that overexpression of Net decreased the expression of c-fos and inhibited pancreatic cancer cell proliferation. Cell cycle analysis demonstrated that Net overexpression inhibited cell cycle progression. These findings suggested that loss of Net repression could augment c-fos expression and further trigger neoplastic cell proliferation, which was involved in the pathogenesis of pancreatic cancer. Therefore, Net might be a potential target for the treatment of c-fos-positive pancreatic cancer.

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

“…Cell viability was assessed via MTT test as previously described [27]. The absorbance of the samples was measured using a microplate reader at 570 nm.…”

“…Soft agar colony formation assay was used to assess the anchorage-independent growth ability of cells as previously described [27]. Agarose (0.6%) in DMEM was casted on six-well plates.…”

“…Our previous preliminary study found that Net overexpression inhibited synthesis of the proto-oncogene c-fos in pancreatic carcinoma BxPC-3 cell [27]. In the present study, we examined the expression of Net in human pancreatic ductal adenocarcinoma and paired normal adjacent tissues, as well as in pancreatic cancer cell lines, and investigated the effect of Net expression on pancreatic ductal adenocarcinoma cell growth, proliferation and apoptosis in vitro and in vivo assays.…”

Elk3 is essential for the progression from progenitor to definitive neural crest cell

“…Elk3 is known to function as a transcriptional repressor that is required for wound healing, tumor growth and angiogenesis in mouse models, and also functions as an anti-oncogenic factor in some cancers (Li et al, 2008; Nakade et al, 2004; Zheng et al, 2003). Here, we show that during development, Elk3 is expressed in the cranial mesenchyme and the neural folds at the onset of neural crest specification as well as in migratory crest cells at later stages.…”

“…Elk3 is a transcriptional repressor that has been linked to cancer metastasis (Li et al, 2008; Sloan et al, 2009), wound healing, and vasculogenesis in cell lines and in mice (Ayadi et al, 2001b; Nozaki et al, 1996; Zheng et al, 2003). However, little is known about its role in normal embryonic development, although in vitro studies have suggested a role in cell migration (Buchwalter et al, 2005).…”