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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 upregulation was identified in ESCC specimens and correlated with poor prognosis of patients. (A) Pin1 protein of 56 clinical ESCC tumor and corresponding non-tumor tissues was examined (top panel). The bar chart showed the patient number according to the relative Pin1 expression in tumor part which was normalized to the corresponding non-tumor part (bottom panel). (B)Pin1 mRNA level of 42 clinical ESCC tumor and corresponding non-tumor tissues was examined (top panel). The bar chart showed the patient number according to the relative Pin1 mRNA in tumor part which was normalized to non-tumor part (bottom panel). (C) Pin1 expression of 89 ESCC tumors was examined by IHC. Expression was scored according to the percentage of positively stained cells and intensity of staining (top panel). The bar chart showed the patient number according to Pin1 expression by IHC scoring (bottom panel). (D) Overall survival of patients was calculated by Kaplan-Meier method and compared with log-rank test. Patients with high Pin1 expression has lower survival rate (p < 0.001). (E) The overall survival of 55 patients with stage I and II disease were stratified by Pin1 expression. Patients with high Pin1 expression had lower survival rate (p < 0.001).
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Fig2: Pin1 upregulation was identified in ESCC specimens and correlated with poor prognosis of patients. (A) Pin1 protein of 56 clinical ESCC tumor and corresponding non-tumor tissues was examined (top panel). The bar chart showed the patient number according to the relative Pin1 expression in tumor part which was normalized to the corresponding non-tumor part (bottom panel). (B)Pin1 mRNA level of 42 clinical ESCC tumor and corresponding non-tumor tissues was examined (top panel). The bar chart showed the patient number according to the relative Pin1 mRNA in tumor part which was normalized to non-tumor part (bottom panel). (C) Pin1 expression of 89 ESCC tumors was examined by IHC. Expression was scored according to the percentage of positively stained cells and intensity of staining (top panel). The bar chart showed the patient number according to Pin1 expression by IHC scoring (bottom panel). (D) Overall survival of patients was calculated by Kaplan-Meier method and compared with log-rank test. Patients with high Pin1 expression has lower survival rate (p < 0.001). (E) The overall survival of 55 patients with stage I and II disease were stratified by Pin1 expression. Patients with high Pin1 expression had lower survival rate (p < 0.001).

Mentions: Pin1 protein expression of 56 ESCC tumor and corresponding non-tumor tissues was determined. We observed that Pin1 in tumor part was higher in 47 (84%) patients when compared to corresponding non-tumor part (Figure 2A). We further determined Pin1 mRNA level of 42 tumor and corresponding non-tumor specimens. Higher Pin1 mRNA level in tumor was identified in 26 (62%) patients (Figure 2B). These data indicated Pin1 upregulation in tumor part was common in clinical ESCC specimens.Figure 2


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 upregulation was identified in ESCC specimens and correlated with poor prognosis of patients. (A) Pin1 protein of 56 clinical ESCC tumor and corresponding non-tumor tissues was examined (top panel). The bar chart showed the patient number according to the relative Pin1 expression in tumor part which was normalized to the corresponding non-tumor part (bottom panel). (B)Pin1 mRNA level of 42 clinical ESCC tumor and corresponding non-tumor tissues was examined (top panel). The bar chart showed the patient number according to the relative Pin1 mRNA in tumor part which was normalized to non-tumor part (bottom panel). (C) Pin1 expression of 89 ESCC tumors was examined by IHC. Expression was scored according to the percentage of positively stained cells and intensity of staining (top panel). The bar chart showed the patient number according to Pin1 expression by IHC scoring (bottom panel). (D) Overall survival of patients was calculated by Kaplan-Meier method and compared with log-rank test. Patients with high Pin1 expression has lower survival rate (p < 0.001). (E) The overall survival of 55 patients with stage I and II disease were stratified by Pin1 expression. Patients with high Pin1 expression had lower survival rate (p < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig2: Pin1 upregulation was identified in ESCC specimens and correlated with poor prognosis of patients. (A) Pin1 protein of 56 clinical ESCC tumor and corresponding non-tumor tissues was examined (top panel). The bar chart showed the patient number according to the relative Pin1 expression in tumor part which was normalized to the corresponding non-tumor part (bottom panel). (B)Pin1 mRNA level of 42 clinical ESCC tumor and corresponding non-tumor tissues was examined (top panel). The bar chart showed the patient number according to the relative Pin1 mRNA in tumor part which was normalized to non-tumor part (bottom panel). (C) Pin1 expression of 89 ESCC tumors was examined by IHC. Expression was scored according to the percentage of positively stained cells and intensity of staining (top panel). The bar chart showed the patient number according to Pin1 expression by IHC scoring (bottom panel). (D) Overall survival of patients was calculated by Kaplan-Meier method and compared with log-rank test. Patients with high Pin1 expression has lower survival rate (p < 0.001). (E) The overall survival of 55 patients with stage I and II disease were stratified by Pin1 expression. Patients with high Pin1 expression had lower survival rate (p < 0.001).
Mentions: Pin1 protein expression of 56 ESCC tumor and corresponding non-tumor tissues was determined. We observed that Pin1 in tumor part was higher in 47 (84%) patients when compared to corresponding non-tumor part (Figure 2A). We further determined Pin1 mRNA level of 42 tumor and corresponding non-tumor specimens. Higher Pin1 mRNA level in tumor was identified in 26 (62%) patients (Figure 2B). These data indicated Pin1 upregulation in tumor part was common in clinical ESCC specimens.Figure 2

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