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Pin1 positively affects tumorigenesis of esophageal squamous cell carcinoma and correlates with poor survival of patients.

Lin FC, Lee YC, Goan YG, Tsai CH, Yao YC, Cheng HC, Lai WW, Wang YC, Sheu BS, Lu PJ - J. Biomed. Sci. (2014)

Bottom Line: Pin1 promotes oncogenesis by regulating multiple oncogenic signaling.When compared to the corresponding non-tumor part, Pin1 protein and mRNA levels in tumor part were higher in 84% and 62% patients, respectively.Furthermore, the association between expression of Pin1 and levels of β-catenin and cyclin D in cell line and clinical specimens was evaluated. β-catenin and cyclin D1 were decreased in CE81T cells with Pin1 knockdown.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan. pjlu2190@mail.ncku.edu.tw.

ABSTRACT

Background: Pin1 promotes oncogenesis by regulating multiple oncogenic signaling. In this study, we investigated the involvement of Pin1 in tumor progression and in the prognosis of human esophageal squamous cell carcinoma (ESCC).

Results: We observed that proliferation, clonogenicity and tumorigenesis of CE81T cells were inhibited by Pin1 knockdown. We next analyzed Pin1 expression in clinical ESCC specimens. When compared to the corresponding non-tumor part, Pin1 protein and mRNA levels in tumor part were higher in 84% and 62% patients, respectively. By immunohistochemistry, we identified that high Pin1 expression was associated with higher primary tumor stage (p = 0.035), higher overall cancer stage (p = 0.047) and poor overall survival (p < 0.001). Furthermore, the association between expression of Pin1 and levels of β-catenin and cyclin D in cell line and clinical specimens was evaluated. β-catenin and cyclin D1 were decreased in CE81T cells with Pin1 knockdown. Cyclin D1 level correlated with Pin1 expression in clinical ESCC specimens.

Conclusions: Pin1 upregulation was associated with advanced stage and poor prognosis of ESCC. Pin1 knockdown inhibited aggressiveness of ESCC cells. β-catenin and cyclin D1 were positively regulated by Pin1. These results indicated that targeting Pin1 pathway could represent a potential modality for treating ESCC.

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Pin1 knockdown inhibited proliferation, clonogenicity and tumorigenesis of ESCC. (A) Pin1 was knocked down in CE81T. Downregulation of Pin1 protein and mRNA was confirmed. (B) In MTT assay, cell proliferation was attenuated after Pin1 knockdown. (C) In colony forming assay, the colony number was reduced after Pin1 knockdown. ** and *** denote to p <0.01 and p <0.001, respectively. (D) In xenograft tumor model, tumor size of cells with Pin1 knockdown was smaller than that of parental CE81T cells.
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Fig1: Pin1 knockdown inhibited proliferation, clonogenicity and tumorigenesis of ESCC. (A) Pin1 was knocked down in CE81T. Downregulation of Pin1 protein and mRNA was confirmed. (B) In MTT assay, cell proliferation was attenuated after Pin1 knockdown. (C) In colony forming assay, the colony number was reduced after Pin1 knockdown. ** and *** denote to p <0.01 and p <0.001, respectively. (D) In xenograft tumor model, tumor size of cells with Pin1 knockdown was smaller than that of parental CE81T cells.

Mentions: We knocked down Pin1 in CE81T cells. Downregulation of Pin1 protein and mRNA was confirmed (Figure 1A). MTT assay showed that proliferation of cells with Pin1 knockdown was attenuated (Figure 1B). The colony number of cells with Pin1 knockdown was significantly less than that of parental CE81T cells (p <0.01). The clonogenicity of clone 48 cells with lower Pin1 level was lower than clone 47 cells (Figure 1C). This result indicated that Pin1 knockdown inhibited growth of ESCC cells in a dose-dependent manner. Furthermore, we developed xenograft tumor with cells injected in subcutis of nude mice. The tumor size from cells with Pin1 knockdown was smaller than that from parental CE81T cells (Figure 1D). These results indicated that Pin1 knockdown inhibited proliferation, clonogenicity and tumorigenesis of ESCC cells.Figure 1


Pin1 positively affects tumorigenesis of esophageal squamous cell carcinoma and correlates with poor survival of patients.

Lin FC, Lee YC, Goan YG, Tsai CH, Yao YC, Cheng HC, Lai WW, Wang YC, Sheu BS, Lu PJ - J. Biomed. Sci. (2014)

Pin1 knockdown inhibited proliferation, clonogenicity and tumorigenesis of ESCC. (A) Pin1 was knocked down in CE81T. Downregulation of Pin1 protein and mRNA was confirmed. (B) In MTT assay, cell proliferation was attenuated after Pin1 knockdown. (C) In colony forming assay, the colony number was reduced after Pin1 knockdown. ** and *** denote to p <0.01 and p <0.001, respectively. (D) In xenograft tumor model, tumor size of cells with Pin1 knockdown was smaller than that of parental CE81T cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4256813&req=5

Fig1: Pin1 knockdown inhibited proliferation, clonogenicity and tumorigenesis of ESCC. (A) Pin1 was knocked down in CE81T. Downregulation of Pin1 protein and mRNA was confirmed. (B) In MTT assay, cell proliferation was attenuated after Pin1 knockdown. (C) In colony forming assay, the colony number was reduced after Pin1 knockdown. ** and *** denote to p <0.01 and p <0.001, respectively. (D) In xenograft tumor model, tumor size of cells with Pin1 knockdown was smaller than that of parental CE81T cells.
Mentions: We knocked down Pin1 in CE81T cells. Downregulation of Pin1 protein and mRNA was confirmed (Figure 1A). MTT assay showed that proliferation of cells with Pin1 knockdown was attenuated (Figure 1B). The colony number of cells with Pin1 knockdown was significantly less than that of parental CE81T cells (p <0.01). The clonogenicity of clone 48 cells with lower Pin1 level was lower than clone 47 cells (Figure 1C). This result indicated that Pin1 knockdown inhibited growth of ESCC cells in a dose-dependent manner. Furthermore, we developed xenograft tumor with cells injected in subcutis of nude mice. The tumor size from cells with Pin1 knockdown was smaller than that from parental CE81T cells (Figure 1D). These results indicated that Pin1 knockdown inhibited proliferation, clonogenicity and tumorigenesis of ESCC cells.Figure 1

Bottom Line: Pin1 promotes oncogenesis by regulating multiple oncogenic signaling.When compared to the corresponding non-tumor part, Pin1 protein and mRNA levels in tumor part were higher in 84% and 62% patients, respectively.Furthermore, the association between expression of Pin1 and levels of β-catenin and cyclin D in cell line and clinical specimens was evaluated. β-catenin and cyclin D1 were decreased in CE81T cells with Pin1 knockdown.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, 138 Sheng-Li Road, Tainan 70403, Taiwan. pjlu2190@mail.ncku.edu.tw.

ABSTRACT

Background: Pin1 promotes oncogenesis by regulating multiple oncogenic signaling. In this study, we investigated the involvement of Pin1 in tumor progression and in the prognosis of human esophageal squamous cell carcinoma (ESCC).

Results: We observed that proliferation, clonogenicity and tumorigenesis of CE81T cells were inhibited by Pin1 knockdown. We next analyzed Pin1 expression in clinical ESCC specimens. When compared to the corresponding non-tumor part, Pin1 protein and mRNA levels in tumor part were higher in 84% and 62% patients, respectively. By immunohistochemistry, we identified that high Pin1 expression was associated with higher primary tumor stage (p = 0.035), higher overall cancer stage (p = 0.047) and poor overall survival (p < 0.001). Furthermore, the association between expression of Pin1 and levels of β-catenin and cyclin D in cell line and clinical specimens was evaluated. β-catenin and cyclin D1 were decreased in CE81T cells with Pin1 knockdown. Cyclin D1 level correlated with Pin1 expression in clinical ESCC specimens.

Conclusions: Pin1 upregulation was associated with advanced stage and poor prognosis of ESCC. Pin1 knockdown inhibited aggressiveness of ESCC cells. β-catenin and cyclin D1 were positively regulated by Pin1. These results indicated that targeting Pin1 pathway could represent a potential modality for treating ESCC.

Show MeSH
Related in: MedlinePlus