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Overexpression of cyclin B1 antagonizes chemotherapeutic-induced apoptosis through PTEN/Akt pathway in human esophageal squamous cell carcinoma cells.

ABSTRACT: The role of cyclin B1 in the clinical therapeutic sensitivity of human esophageal squamous cell carcinoma (ESCC) remains to be defined. In this study, we found that elevated cyclin B1 expression attenuated the apoptosis induced by cisplatin or paclitaxel, while knockdown of cyclin B1 enhanced cisplatin or paclitaxel sensitivity in ESCC cells. Cyclin B1-mediated apoptosis may rely on the Bcl-2-dependent mitochondria-regulated intrinsic death pathway, and the antagonizing effect of cyclin B1 on chemotherapeutic agent-induced apoptosis was through PTEN/Akt pathway. Therefore, cyclin B1 might be a therapeutic target for the development of specific and efficient approaches in the treatment of ESCC.

SUBMITTER: Ou Y

PROVIDER: S-EPMC3566051 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Overexpression of cyclin B1 antagonizes chemotherapeutic-induced apoptosis through PTEN/Akt pathway in human esophageal squamous cell carcinoma cells.

Ou Yunwei Y Ma Liying L Ma Ling L Huang Zhen Z Zhou Wei W Zhao Chunling C Zhang Bailin B Song Yongmei Y Yu Chunjiang C Zhan Qimin Q

Cancer biology & therapy 20121031 1

The role of cyclin B1 in the clinical therapeutic sensitivity of human esophageal squamous cell carcinoma (ESCC) remains to be defined. In this study, we found that elevated cyclin B1 expression attenuated the apoptosis induced by cisplatin or paclitaxel, while knockdown of cyclin B1 enhanced cisplatin or paclitaxel sensitivity in ESCC cells. Cyclin B1-mediated apoptosis may rely on the Bcl-2-dependent mitochondria-regulated intrinsic death pathway, and the antagonizing effect of cyclin B1 on ch ...[more]

PMID: 23114644

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Project description:Hsp90α (heat shock protein 90α), one of the important molecular chaperones in cancer cell signal transduction, has been a new candidate target for cancer therapy. Cyclin B1, the client protein of Hsp90α, plays a key role as a mitotic cyclin in the G2-M phase transition during the cell cycle progression. However, the relationship between the level of HSP90α and cyclin B1, the location of Hsp90α and cyclin B1 in prognosis of esophageal squamous cell carcinoma (ESCC) has not been examined. Here, we demonstrate that the diagnostic significance of Hsp90α and cyclin B1 by immunohistochemistry and the association of Hsp90α and cyclin B1 expression in ESCC. In the specimens from 105 ESCC patients (81 stained with Hsp90α antibody by Immunohistochemistry, 65 with cyclin B1 antibody, and among them, 41 paired specimens were stained with Hsp90α and cyclin B1 respectively, and then checked for the correlation of the level and location of Hsp90α and cylcin B1. The positivity rate of Hsp90α and cyclin B1 expression were 96.3% (78 of 81) and 84.6% (55 of 65) respectively. Both of them, the expression levels are associated with the clinical pathological stage (Hsp90α, p=0.027; cyclin B1, p=0.007). No association was found between Hsp90α or cyclin B1 and gender, age, tumor location. As to TMN stage, there is no association with the level of Hsp90α, However, cyclin B1 expression is significantly related to tumor status (p=0.002). Interestingly, Hsp90α expression was negatively correlated to cyclin B1 expression (Gamma=-0.692, p=0.007) in the keratin pearls though there is a positive correlation in the other areas of tumor (Gamma=0.503, p=0.015), which suggest Hsp90α might play diverse roles in the cyclin B1 expression and cyclin B1 related cell cycle regulation in the different area of tumor. These findings demonstrated that the expression of Hsp90α, cyclin B1 protein is associated with tumor malignancy and prognosis for patients with human esophageal squamous cell carcinoma, and Hsp90α might be involved in cyclin B1 expression regulation and cell cycle regulation in keratin peal formation of ESCC.

Dataset Information

Overexpression of cyclin B1 antagonizes chemotherapeutic-induced apoptosis through PTEN/Akt pathway in human esophageal squamous cell carcinoma cells.

Publications

Overexpression of cyclin B1 antagonizes chemotherapeutic-induced apoptosis through PTEN/Akt pathway in human esophageal squamous cell carcinoma cells.

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