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High levels of KAP1 expression are associated with aggressive clinical features in ovarian cancer.

Cui Y, Yang S, Fu X, Feng J, Xu S, Ying G - Int J Mol Sci (2014)

Bottom Line: Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer.KAP1 expression correlated significantly with clinical stage (χ2 = 14.57, p < 0.0001), pathological grade (χ2 = 6.06, p = 0.048) and metastases (χ2 =10.38, p = 0.001).High KAP1 expression was a prognostic factor of ovarian cancer.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cancer Cell Biology, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. cuiyanfen@163.com.

ABSTRACT
KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 patients with ovarian epithelial cancer, 15 with ovarian borderline tumor, and 20 normal ovarian tissue. The correlations of KAP1 expression with clinicopathological features were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer. The positive rates of KAP1 were significantly higher in ovarian epithelial cancer (55.7%) and borderline tumor (20.0%) than in normal ovarian tissue (5.0%) (all p < 0.01). KAP1 expression correlated significantly with clinical stage (χ2 = 14.57, p < 0.0001), pathological grade (χ2 = 6.06, p = 0.048) and metastases (χ2 =10.38, p = 0.001). Patients with high KAP 1 levels showed poor survival (p < 0.0001). Multivariate analysis showed that KAP1 high expression was an independent predictor for ovarian cancer patients (hazard ratio = 0.463; 95% confidence interval = 0.230-0.9318, p = 0.031). Functionally, depletion of KAP1 by siRNA inhibited ovarian cancer cell proliferation, cell migration. KAP1 expression correlated with aggressive clinical features in ovarian cancer. High KAP1 expression was a prognostic factor of ovarian cancer.

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Downregulated expression of KAP1 inhibits cell growth and migration in A2780 cells. (A) western blot indicates the KAP1 interference efficiency; (B) MTT assay at 0, 24, 48, 72 and 96 h after transfection; (C) representative images of two-dimensional culture of cells; (D) representative images of soft agar colony formation assay of cells (100×); (E) photographs represent cells migrated into the wounded area, and histogram shows the relative migration distance of cells in the wound-healing assay (200×) and (F) transwell migration assay (100×). (*p < 0.05; **p < 0.01; *** p < 0.001).
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ijms-16-00363-f006: Downregulated expression of KAP1 inhibits cell growth and migration in A2780 cells. (A) western blot indicates the KAP1 interference efficiency; (B) MTT assay at 0, 24, 48, 72 and 96 h after transfection; (C) representative images of two-dimensional culture of cells; (D) representative images of soft agar colony formation assay of cells (100×); (E) photographs represent cells migrated into the wounded area, and histogram shows the relative migration distance of cells in the wound-healing assay (200×) and (F) transwell migration assay (100×). (*p < 0.05; **p < 0.01; *** p < 0.001).

Mentions: Because KAP1 was obviously overexpressed in advanced stage ovarian cancer, we investigated the effect of KAP 1 on ovarian cancer cell growth and anchorage- independent growth. siRNA was used to deplete expression of KAP1 in ovarian cancer cell lines SKOV3 and A2780 (Figure 5A and Figure 6A). The MTT cell proliferation assay demonstrated that lowering KAP1 expression significantly inhibited ovarian cancer cell growth by 50% in the SKOV3 siKAP1 group (p < 0.01), and 60% in the A2780 siKAP1 group (p < 0.001) when compared with the control group (Figure 5B and Figure 6B). The stable KAP1 knockdown in SKOV3 cell line exhibited a two to three-fold decrease in cell growth based on the focus formation assay (p < 0.01) (Figure 5C) and a three to four-fold decrease in colony formation using the anchorage-independent growth assay (p < 0.01) (Figure 5D), and similar results were found in the A2780 cell line, (Figure 6C,D). In summary, these findings suggest that KAP1 can promote both the anchorage-dependent and -independent growth of ovarian cancer cells.


High levels of KAP1 expression are associated with aggressive clinical features in ovarian cancer.

Cui Y, Yang S, Fu X, Feng J, Xu S, Ying G - Int J Mol Sci (2014)

Downregulated expression of KAP1 inhibits cell growth and migration in A2780 cells. (A) western blot indicates the KAP1 interference efficiency; (B) MTT assay at 0, 24, 48, 72 and 96 h after transfection; (C) representative images of two-dimensional culture of cells; (D) representative images of soft agar colony formation assay of cells (100×); (E) photographs represent cells migrated into the wounded area, and histogram shows the relative migration distance of cells in the wound-healing assay (200×) and (F) transwell migration assay (100×). (*p < 0.05; **p < 0.01; *** p < 0.001).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4307251&req=5

ijms-16-00363-f006: Downregulated expression of KAP1 inhibits cell growth and migration in A2780 cells. (A) western blot indicates the KAP1 interference efficiency; (B) MTT assay at 0, 24, 48, 72 and 96 h after transfection; (C) representative images of two-dimensional culture of cells; (D) representative images of soft agar colony formation assay of cells (100×); (E) photographs represent cells migrated into the wounded area, and histogram shows the relative migration distance of cells in the wound-healing assay (200×) and (F) transwell migration assay (100×). (*p < 0.05; **p < 0.01; *** p < 0.001).
Mentions: Because KAP1 was obviously overexpressed in advanced stage ovarian cancer, we investigated the effect of KAP 1 on ovarian cancer cell growth and anchorage- independent growth. siRNA was used to deplete expression of KAP1 in ovarian cancer cell lines SKOV3 and A2780 (Figure 5A and Figure 6A). The MTT cell proliferation assay demonstrated that lowering KAP1 expression significantly inhibited ovarian cancer cell growth by 50% in the SKOV3 siKAP1 group (p < 0.01), and 60% in the A2780 siKAP1 group (p < 0.001) when compared with the control group (Figure 5B and Figure 6B). The stable KAP1 knockdown in SKOV3 cell line exhibited a two to three-fold decrease in cell growth based on the focus formation assay (p < 0.01) (Figure 5C) and a three to four-fold decrease in colony formation using the anchorage-independent growth assay (p < 0.01) (Figure 5D), and similar results were found in the A2780 cell line, (Figure 6C,D). In summary, these findings suggest that KAP1 can promote both the anchorage-dependent and -independent growth of ovarian cancer cells.

Bottom Line: Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer.KAP1 expression correlated significantly with clinical stage (χ2 = 14.57, p < 0.0001), pathological grade (χ2 = 6.06, p = 0.048) and metastases (χ2 =10.38, p = 0.001).High KAP1 expression was a prognostic factor of ovarian cancer.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cancer Cell Biology, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China. cuiyanfen@163.com.

ABSTRACT
KAP1 is an universal corepressor for Kruppel-associated box zinc finger proteins in both normal and tumor cells. In this study, the biological function and clinical significance of KAP1 expression in ovarian cancer were investigated. Immunohistological staining of KAP1 was evaluated in 111 patients with ovarian epithelial cancer, 15 with ovarian borderline tumor, and 20 normal ovarian tissue. The correlations of KAP1 expression with clinicopathological features were studied. Kaplan-Meier analysis and Cox proportional hazard modeling were used to assess overall survival to analyze the effect of KAP1 expression on the prognosis of ovarian cancer. The positive rates of KAP1 were significantly higher in ovarian epithelial cancer (55.7%) and borderline tumor (20.0%) than in normal ovarian tissue (5.0%) (all p < 0.01). KAP1 expression correlated significantly with clinical stage (χ2 = 14.57, p < 0.0001), pathological grade (χ2 = 6.06, p = 0.048) and metastases (χ2 =10.38, p = 0.001). Patients with high KAP 1 levels showed poor survival (p < 0.0001). Multivariate analysis showed that KAP1 high expression was an independent predictor for ovarian cancer patients (hazard ratio = 0.463; 95% confidence interval = 0.230-0.9318, p = 0.031). Functionally, depletion of KAP1 by siRNA inhibited ovarian cancer cell proliferation, cell migration. KAP1 expression correlated with aggressive clinical features in ovarian cancer. High KAP1 expression was a prognostic factor of ovarian cancer.

Show MeSH
Related in: MedlinePlus