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Net expression inhibits the growth of pancreatic ductal adenocarcinoma cell PL45 in vitro and in vivo.

Li B, Wan X, Zhu Q, Li L, Zeng Y, Hu D, Qian Y, Lu L, Wang X, Meng X - PLoS ONE (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

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.

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Net induces the apoptosis in pancreatic ductal carcinoma cell PL45.(A) Cell apoptosis was examined in PL45 cells after 48 hours of Ad5/F35-Net transfection using AnnexinV/PI method. (B) The rates of early and late apoptosis were evaluated after 48 hours of Ad5/F35-Net transfection. (C) Ultrastructures of cells were observed by transmission electron microscope. Concentrated phenomena of cytoplasm, karyopyknosis, karyorrhexis and apoptotic body formation were detected in PL45 cell transfected with Ad5/F35-Net, no obvious changes was observed in control group and Ad5/F35-GFP group. Black arrow indicated karyopyknosis andkaryorrhexis. *p<0.05, **p<0.01.
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pone-0057818-g003: Net induces the apoptosis in pancreatic ductal carcinoma cell PL45.(A) Cell apoptosis was examined in PL45 cells after 48 hours of Ad5/F35-Net transfection using AnnexinV/PI method. (B) The rates of early and late apoptosis were evaluated after 48 hours of Ad5/F35-Net transfection. (C) Ultrastructures of cells were observed by transmission electron microscope. Concentrated phenomena of cytoplasm, karyopyknosis, karyorrhexis and apoptotic body formation were detected in PL45 cell transfected with Ad5/F35-Net, no obvious changes was observed in control group and Ad5/F35-GFP group. Black arrow indicated karyopyknosis andkaryorrhexis. *p<0.05, **p<0.01.

Mentions: The apoptosis of PL45 cell was evaluated by AnnexinV/PI staining method after 48 hours of Ad5/F35-Net transfection. The early period apoptosis potential of control cells, cells transfected with Ad5/F35-GFP or Ad5/F35-Net group was 5.81±1.6%, 5.90%±1.3 and 46.32±8.1% respectively. The differences between Ad5/F35-Net and control or Ad5/F35-GFP group were significant (P<0.01), while there was no significant difference between control and Ad5/F35-GFP group (P>0.05). The enhanced apoptotic ability of cell transfected with Ad5/F35-Net occurred in the early stage but not in the late stage, there were no statistical difference in the late stage of apoptosis among three groups (32.32±4.1%, 32.61%±4.4 and 34.64±4.7%, respectively. Fig. 3A, 3B). Ultrastructures of cells were observed by TEM (Transmission Electron Microscope) after transfection. We found that PL45 cell transfected with Ad5/F35-Net demonstrated concentrated phenomena of cytoplasm, density increasing, nuclear chromatin margination, karyopyknosis and karyorrhexis, apoptotic body formation, while no obvious changes was observed in neither control group or Ad5/F35-GFP group (Fig. 3C). Our results suggested that overexpression of Net induced the apoptosis of PL45 cell.


Net expression inhibits the growth of pancreatic ductal adenocarcinoma cell PL45 in vitro and in vivo.

Li B, Wan X, Zhu Q, Li L, Zeng Y, Hu D, Qian Y, Lu L, Wang X, Meng X - PLoS ONE (2013)

Net induces the apoptosis in pancreatic ductal carcinoma cell PL45.(A) Cell apoptosis was examined in PL45 cells after 48 hours of Ad5/F35-Net transfection using AnnexinV/PI method. (B) The rates of early and late apoptosis were evaluated after 48 hours of Ad5/F35-Net transfection. (C) Ultrastructures of cells were observed by transmission electron microscope. Concentrated phenomena of cytoplasm, karyopyknosis, karyorrhexis and apoptotic body formation were detected in PL45 cell transfected with Ad5/F35-Net, no obvious changes was observed in control group and Ad5/F35-GFP group. Black arrow indicated karyopyknosis andkaryorrhexis. *p<0.05, **p<0.01.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585156&req=5

pone-0057818-g003: Net induces the apoptosis in pancreatic ductal carcinoma cell PL45.(A) Cell apoptosis was examined in PL45 cells after 48 hours of Ad5/F35-Net transfection using AnnexinV/PI method. (B) The rates of early and late apoptosis were evaluated after 48 hours of Ad5/F35-Net transfection. (C) Ultrastructures of cells were observed by transmission electron microscope. Concentrated phenomena of cytoplasm, karyopyknosis, karyorrhexis and apoptotic body formation were detected in PL45 cell transfected with Ad5/F35-Net, no obvious changes was observed in control group and Ad5/F35-GFP group. Black arrow indicated karyopyknosis andkaryorrhexis. *p<0.05, **p<0.01.
Mentions: The apoptosis of PL45 cell was evaluated by AnnexinV/PI staining method after 48 hours of Ad5/F35-Net transfection. The early period apoptosis potential of control cells, cells transfected with Ad5/F35-GFP or Ad5/F35-Net group was 5.81±1.6%, 5.90%±1.3 and 46.32±8.1% respectively. The differences between Ad5/F35-Net and control or Ad5/F35-GFP group were significant (P<0.01), while there was no significant difference between control and Ad5/F35-GFP group (P>0.05). The enhanced apoptotic ability of cell transfected with Ad5/F35-Net occurred in the early stage but not in the late stage, there were no statistical difference in the late stage of apoptosis among three groups (32.32±4.1%, 32.61%±4.4 and 34.64±4.7%, respectively. Fig. 3A, 3B). Ultrastructures of cells were observed by TEM (Transmission Electron Microscope) after transfection. We found that PL45 cell transfected with Ad5/F35-Net demonstrated concentrated phenomena of cytoplasm, density increasing, nuclear chromatin margination, karyopyknosis and karyorrhexis, apoptotic body formation, while no obvious changes was observed in neither control group or Ad5/F35-GFP group (Fig. 3C). Our results suggested that overexpression of Net induced the apoptosis of PL45 cell.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology, Shanghai First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

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.

Show MeSH
Related in: MedlinePlus