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Overexpression of BLCAP induces S phase arrest and apoptosis independent of p53 and NF-κB in human tongue carcinoma

BLCAP overexpression induces S phase arrest and apoptosis

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Abstract

Bladder cancer-associated protein gene (BLCAP) is a novel candidate tumor suppressor gene identified from the human bladder carcinoma. Our previous studies have shown that BLCAP overexpression could inhibit cell growth by inducing apoptosis in HeLa cells [Zuo Z, Zhao M, Liu J, Gao G, Wu X: Tumor Biol 27: 221–226, 2006]. Such evidence suggests the alterations in BLCAP may play an important role in tumorigenesis. To further study the biological function of the BLCAP gene, we constructed a recombinant retroviral vector encoding BLCAP cDNA. Overexpressed BLCAP, via stable infection of exogenous BLCAP, resulted in growth inhibition of the human tongue cancer cell line Tca8113 in vitro, accompanied by S phase cell cycle arrest and apoptosis. The growth inhibition was correlated with up-regulation of p21WAF1/CIP1 expression and down-regulation of Bcl-XL and Bcl-2 expressions. However, p53 expression and NF-κB activity remained unchanged post infection. Furthermore, no changes in p53 phosphorylation at Ser46 and nuclear localization, which are critical to p53 function, were observed in BLCAP-overexpressed cells. Taken together, BLCAP may play a role not only in regulating cell proliferation but also in coordinating apoptosis and cell cycle via a novel way independent of p53 and NF-κB.

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Abbreviations

BLCAP:

bladder cancer-associated protein gene

NF-κB:

nuclear factor kappa B

Bcl-2:

B-cell lymphocytic-leukaemia proto-oncogene 2

MTT:

methylthiazole tetrazolium

EMSA:

electrophoretic mobility shift assay

DMSO:

dimethyl sulphoxide

SCCHN:

squamous cell carcinoma of the head and neck

PI:

propidium iodide

PVDF:

polyvinylidene difluoride

CDK:

cyclin-dependent kinase

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Acknowledgment

This project was supported by the National Natural Science Foundation of China (No. 30250008).

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Correspondence to Xinxing Wu.

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Jun Yao and Li Duan contributed equally to this work.

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Yao, J., Duan, L., Fan, M. et al. Overexpression of BLCAP induces S phase arrest and apoptosis independent of p53 and NF-κB in human tongue carcinoma. Mol Cell Biochem 297, 81–92 (2007). https://doi.org/10.1007/s11010-006-9332-2

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  • DOI: https://doi.org/10.1007/s11010-006-9332-2

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