Significance of E2F-1 overexpression in epithelial ovarian cancer

Suh, Dong‐Soo; Yoon, Man Soo; Choi, Kyung Un; Kim, J. Y.

doi:10.1111/j.1525-1438.2007.01044.x

Cited by 33 publications

(24 citation statements)

References 26 publications

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“…[42][43][44][45] Our results showed that the expression of E2F1 was regulated by miR-26a and HMGA2. It has been reported that E2F1 is overexpressed in CDDP-resistant cell lines, and decreased expression of E2F1 sensitizes cancer cells to chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 62%

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Yang

Zhang

Zhao

et al. 2015

Cancer Biology & Therapy

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Background: Lung cancer is the most common cancer that is caused by perturbation of regulatory pathways rather than dysfunction of a single gene. Cisplatin (CDDP; cis-diamminedichloroplatinum II) is the first member of a class of platinum-containing anti-cancer medication, which binds to DNA and triggers apoptosis. CDDP-based chemotherapy is used to treat various types of cancers. However, the efficacy of CDDP in the treatment of non-small-cell lung cancer (NSCLC) is limited by acquired drug resistance. MicroRNAs have recently emerged as key regulators of cancers, and miR-26a is one of downregulated miRNAs in A549/CDDP res cell line. This study aimed to investigate the role of miR-26a in CDDP resistance in NSCLC as well as the underlying mechanisms.Methods: In this study, we analyzed expressional profiles of CDDP resistance-related mRNA, miRNA, and transcription factors (TF) that regulate miRNA expression in NSCLC. A549 cells were treated with CDDP, miR-26a mimic, or miR-26a inhibitor, and followed by biological analysis including drug sensitivity assay, colony formation assay, terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) assay, and cell cycle analysis. Luciferase assay was used to determine the target of miR-26a. The regulation of miR-26a in Akt pathway was measured by western blot.Results: High mobility group A (HMGA) 2 was identified as the target of miR-26a. Overexpression of miR26a in A549 cells inhibited G1-S transition, increased cell death in response to CDDP treatment, and decreased the colony formation of A549 cells. MiR-26a significantly decreased the expression of E2F1, diminished Akt phosphorylation, and downregulated Bcl2 expression. Cell growth was suppressed by inhibiting HMGA2-mediated E2F1-Akt pathway.Conclusion: MiR-26a is responsible for A549 cell sensitivity in the treatment of CDDP through regulating HMGA2-mediated E2F1-Akt pathway.

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Section: Discussionmentioning

confidence: 62%

Decreased MicroRNA-26a expression causes cisplatin resistance in human non-small cell lung cancer

Yang

Zhang

Zhao

et al. 2015

Cancer Biology & Therapy

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“…E2F-1 immunohistochemical expression was correlated with increased tumor cell apoptosis, suggesting that E2F-1 may have an oncosuppressor role in HCC. An apoptosis promoting tumor suppressor role for E2F-1 has also been demonstrated in adenocarcinoma of Barrett esophagus, in carcinomas of colon, prostate, and bladder, and more recently, in osteosarcoma [8,9,[20][21][22]. In contrast, E2F-1 appears to act as an oncogene, promoting tumor growth, in lung cancer, esophageal squamous cell carcinoma, and carcinomas of the breast, pancreas, and ovary [9,23,24].…”

Section: Discussionmentioning

confidence: 85%

E2F-1 is overexpressed and pro-apoptotic in human hepatocellular carcinoma

et al. 2012

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E2F-1 is a transcription factor involved in DNA synthesis and repair, cell proliferation, and apoptosis. Hyposphorylated pRb represses E2F-1 action in early G1 phase, while in late G1, pRb hyperphosphorylation leads to E2F-1 release and activation. In vitro studies have shown that E2F-1 may act either as oncogene or as tumor suppressor gene. We evaluated immunohistochemical expression of E2F-1 protein in chronic viral liver disease and hepatocellular carcinoma (HCC) and correlated this with clinicopathological parameters, cell proliferation, apoptosis, and the expression of E2F-1-regulators, pRb, and phospho-pRb (Ser795). In liver biopsies from 30 patients with chronic viral hepatitis, including 22 with cirrhosis without HCC, and 57 with cirrhosis with HCC, E2F-1 expression was assessed by immunohistochemistry. In chronic hepatitis and cirrhosis, hepatocytes and cholangiocytes demonstrated mild cytoplasmic and/or nuclear membrane E2F-1 immunostaining. In contrast, all HCC (100 %) showed strong nuclear E2F-1 immunostaining, with or without membrane accentuation, while a minority demonstrated additional moderate cytoplasmic immunostaining. Abnormally low pRb and phospho-pRb expression was seen in 70 % and 67.9 % of HCC, respectively. In HCC, nuclear E2F-1 expression was inversely correlated with phospho-pRb expression (p = 0.001) and positively related to tumor apoptotic index (p = 0.025). No significant correlation was found between E2F-1 expression and patient demographics, HCC etiology, tumor grade, pRb, p53 expression, or cell proliferation. In conclusion, we show that the increased expression of E2F-1 protein in human HCC is correlated with enhanced tumor cell apoptosis supporting a pro-apoptotic role of E2F-1 in human HCC.

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“…E2F1 overexpression was found to be an independent poor prognostic variable for survival in a series of 72 patients with EOC (immunostaining 2+ versus 0, 1+, RR = 8.08, 95% CI = 1.36-4.80, p = 0.022) [147]. Real-time polymerase chain reaction (RT-PCR) of all E2F family members in tissue specimens from 77 EOCs showed that low expression of E2F1 or E2F2 as well as high expression of E2F4 or E2F7 predicted longer survival (p = 0.047, 0.006, 0.042, and 0.042, respectively) [148].…”

Section: E2f Trascription Factorsmentioning

confidence: 94%