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Nuclear BAG-1 expression inhibits apoptosis in colorectal adenoma-derived epithelial cells

Nuclear BAG-1 expression inhibits apoptosis in colorectal adenoma-derived epithelial cells
Nuclear BAG-1 expression inhibits apoptosis in colorectal adenoma-derived epithelial cells
BAG-1 is an anti-apoptotic protein that is frequently deregulated in a variety of malignancies including colorectal cancer. There are three isoforms: BAG-1L is located in the nucleus, BAG-1M and BAG-1S are located both in the nucleus and the cytoplasm. In colon cancer, the expression of nuclear BAG-1 is associated with poorer prognosis and is potentially a useful predictive factor for distant metastasis. However, the function of BAG-1 in colonic epithelial cells has not been studied. Having previously shown a predominant nuclear localisation of BAG-1 in adenoma-derived cell lines,1 we wanted to determine the function of nuclear BAG-1 in these non-tumourigenic cells, to identify whether nuclear BAG-1 was implicated in tumour progression in the colon. In the current report we established that nuclear BAG-1 inhibits apoptosis in a colorectal adenoma-derived cell line. We demonstrate that apoptosis induced by ?-radiation or the vitamin D analogue EB1089 in the non-tumourigenic human colorectal adenoma-derived S/RG/C2 cell line, was preceded by a decrease in nuclear and an increase in cytoplasmic BAG-1 expression. This change in subcellular localisation of BAG-1 was due to the redistribution of the BAG-1M isoform. In addition, we have shown that the maintenance of high nuclear BAG-1 through enforced expression of the nuclear localised BAG-1L isoform enhanced cellular survival after ?-radiation or exposure to EB1089. Furthermore the expression of cytoplasmic BAG-1S isoform fused with a nuclear localisation signal protected against ?-radiation induced apoptosis. This demonstrates that nuclear localisation of the BAG-1 protein confers a survival advantage in colorectal adenoma-derived cells and that nuclear BAG-1 could potentially be an important survival factor in colorectal carcinogenesis
apoptosis, BAG-1, chemoprevention, colon cancer
1360-8185
301-311
Barnes, J.D.
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Arhel, N.J.
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Lee, S.S.
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Sharp, A.
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Al-Okail, M.
fe5d9d3d-4d97-4f29-8ee8-64208368a621
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394
Hague, A.
ea2f8822-0c83-4868-a7f0-91e35371e636
Paraskeva, C.
efc0747a-0937-46a3-9929-39a20ea6c28b
Williams, A.C.
24f37520-cb05-45ba-80da-cc4d0211722d
Barnes, J.D.
bf1987a2-432f-4454-81c0-627b9a2f00d0
Arhel, N.J.
0fc90800-6cea-44e1-8212-3dbd17514139
Lee, S.S.
8652e972-2fdc-4005-8ff8-3fb33c5d980d
Sharp, A.
9f94bdc2-3c1c-4520-b874-b8ac8b989512
Al-Okail, M.
fe5d9d3d-4d97-4f29-8ee8-64208368a621
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394
Hague, A.
ea2f8822-0c83-4868-a7f0-91e35371e636
Paraskeva, C.
efc0747a-0937-46a3-9929-39a20ea6c28b
Williams, A.C.
24f37520-cb05-45ba-80da-cc4d0211722d

Barnes, J.D., Arhel, N.J., Lee, S.S., Sharp, A., Al-Okail, M., Packham, G., Hague, A., Paraskeva, C. and Williams, A.C. (2005) Nuclear BAG-1 expression inhibits apoptosis in colorectal adenoma-derived epithelial cells. Apoptosis, 10 (2), 301-311. (doi:10.1007/s10495-005-0804-8).

Record type: Article

Abstract

BAG-1 is an anti-apoptotic protein that is frequently deregulated in a variety of malignancies including colorectal cancer. There are three isoforms: BAG-1L is located in the nucleus, BAG-1M and BAG-1S are located both in the nucleus and the cytoplasm. In colon cancer, the expression of nuclear BAG-1 is associated with poorer prognosis and is potentially a useful predictive factor for distant metastasis. However, the function of BAG-1 in colonic epithelial cells has not been studied. Having previously shown a predominant nuclear localisation of BAG-1 in adenoma-derived cell lines,1 we wanted to determine the function of nuclear BAG-1 in these non-tumourigenic cells, to identify whether nuclear BAG-1 was implicated in tumour progression in the colon. In the current report we established that nuclear BAG-1 inhibits apoptosis in a colorectal adenoma-derived cell line. We demonstrate that apoptosis induced by ?-radiation or the vitamin D analogue EB1089 in the non-tumourigenic human colorectal adenoma-derived S/RG/C2 cell line, was preceded by a decrease in nuclear and an increase in cytoplasmic BAG-1 expression. This change in subcellular localisation of BAG-1 was due to the redistribution of the BAG-1M isoform. In addition, we have shown that the maintenance of high nuclear BAG-1 through enforced expression of the nuclear localised BAG-1L isoform enhanced cellular survival after ?-radiation or exposure to EB1089. Furthermore the expression of cytoplasmic BAG-1S isoform fused with a nuclear localisation signal protected against ?-radiation induced apoptosis. This demonstrates that nuclear localisation of the BAG-1 protein confers a survival advantage in colorectal adenoma-derived cells and that nuclear BAG-1 could potentially be an important survival factor in colorectal carcinogenesis

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Published date: 2005
Keywords: apoptosis, BAG-1, chemoprevention, colon cancer

Identifiers

Local EPrints ID: 26212
URI: https://eprints.soton.ac.uk/id/eprint/26212
ISSN: 1360-8185
PURE UUID: 51c4414e-8d87-4c99-9077-e60637c96ee1
ORCID for G. Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 20 Apr 2006
Last modified: 31 Jan 2019 01:37

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Contributors

Author: J.D. Barnes
Author: N.J. Arhel
Author: S.S. Lee
Author: A. Sharp
Author: M. Al-Okail
Author: G. Packham ORCID iD
Author: A. Hague
Author: C. Paraskeva
Author: A.C. Williams

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