Limits...
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.

Show MeSH

Related in: MedlinePlus

The effects of Net expression on tumor growth in vivo.(A) Tumor size was measured every three days interval in each group. (B) Weight of dissectable xenograft tumors was measured in each group. (C) Expression of Net, c-fos and P21 in mRNA levels in xenograft tissues. (D) Representative H&E staining, histological staining of Net, c-fos and P21, PCNA staining and TUNEL assay in xenogrft tissues. (E) Index of PCNA and apoptosis were accounted in xenograft tumour tissues. *p<0.05, **p<0.01.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3585156&req=5

pone-0057818-g004: The effects of Net expression on tumor growth in vivo.(A) Tumor size was measured every three days interval in each group. (B) Weight of dissectable xenograft tumors was measured in each group. (C) Expression of Net, c-fos and P21 in mRNA levels in xenograft tissues. (D) Representative H&E staining, histological staining of Net, c-fos and P21, PCNA staining and TUNEL assay in xenogrft tissues. (E) Index of PCNA and apoptosis were accounted in xenograft tumour tissues. *p<0.05, **p<0.01.

Mentions: To examine the effect of Net on human pancreatic carcinoma growth in in vivo, xenograft model of human pancreatic carcinoma in nude mice was established. The average tumor size and weight were significantly reduced in nude mice injected with PL45 cells transfected with Ad5/F35-Net 21 days later compared with that in mice injected with control cells or cells transfected with Ad5/F35-GFP (P<0.05, Fig. 4A, 4B) indicating that the overexpression of Net inhibits the growth of pancreatic carcinoma in mice. RT-PCR and Immunohistochemistry assay showed that over-expression of Net resulted in decreased c-fos expression and increased P21 expression both in mRNA and protein levels in xenograft tissues (Fig. 4C, 4D). PCNA stain results demonstrated that PCNA labeling index was significant lower in xenograft tissues with cells transfected with Ad5/F35-Net (42.9%) than that with control cells (74.1%) or cells transfected with Ad5/F35-GFP (68.7%) (P<0.01, Fig. 4E). On the other hand, apoptotic cells detected by TUNEL assay showed that the apoptotic index of xenograft tissues with cells transfected with Ad5/F35-Net(18.2%) was significant higher than that with control cells (5.4%) or cells transfected with Ad5/F35-GFP group (4.9%) (P<0.01, Fig. 4E), which suggested that Net had the ability to prohibit pancreatic carcinoma xenograft growth in nude mice through inhibiting proliferation and inducing cell apoptosis.


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)

The effects of Net expression on tumor growth in vivo.(A) Tumor size was measured every three days interval in each group. (B) Weight of dissectable xenograft tumors was measured in each group. (C) Expression of Net, c-fos and P21 in mRNA levels in xenograft tissues. (D) Representative H&E staining, histological staining of Net, c-fos and P21, PCNA staining and TUNEL assay in xenogrft tissues. (E) Index of PCNA and apoptosis were accounted in xenograft tumour tissues. *p<0.05, **p<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0057818-g004: The effects of Net expression on tumor growth in vivo.(A) Tumor size was measured every three days interval in each group. (B) Weight of dissectable xenograft tumors was measured in each group. (C) Expression of Net, c-fos and P21 in mRNA levels in xenograft tissues. (D) Representative H&E staining, histological staining of Net, c-fos and P21, PCNA staining and TUNEL assay in xenogrft tissues. (E) Index of PCNA and apoptosis were accounted in xenograft tumour tissues. *p<0.05, **p<0.01.
Mentions: To examine the effect of Net on human pancreatic carcinoma growth in in vivo, xenograft model of human pancreatic carcinoma in nude mice was established. The average tumor size and weight were significantly reduced in nude mice injected with PL45 cells transfected with Ad5/F35-Net 21 days later compared with that in mice injected with control cells or cells transfected with Ad5/F35-GFP (P<0.05, Fig. 4A, 4B) indicating that the overexpression of Net inhibits the growth of pancreatic carcinoma in mice. RT-PCR and Immunohistochemistry assay showed that over-expression of Net resulted in decreased c-fos expression and increased P21 expression both in mRNA and protein levels in xenograft tissues (Fig. 4C, 4D). PCNA stain results demonstrated that PCNA labeling index was significant lower in xenograft tissues with cells transfected with Ad5/F35-Net (42.9%) than that with control cells (74.1%) or cells transfected with Ad5/F35-GFP (68.7%) (P<0.01, Fig. 4E). On the other hand, apoptotic cells detected by TUNEL assay showed that the apoptotic index of xenograft tissues with cells transfected with Ad5/F35-Net(18.2%) was significant higher than that with control cells (5.4%) or cells transfected with Ad5/F35-GFP group (4.9%) (P<0.01, Fig. 4E), which suggested that Net had the ability to prohibit pancreatic carcinoma xenograft growth in nude mice through inhibiting proliferation and inducing cell apoptosis.

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