Nuclear BAG-1 expression reflects malignant potential in colorectal carcinomas

Kikuchi, Ryuichi; Noguchi, Tsuyoshi; Takeno, Shinsuke; Funada, Y.; Moriyama, Hideki; Uchida, Yuzo

doi:10.1038/sj.bjc.6600579

Cited by 30 publications

(23 citation statements)

References 19 publications

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“…32 Interestingly in colon cancer, BAG-1 is overexpressed and nuclear BAG-1 expression is associated with poor survival. 7,24 In the current study we have shown that the maintenance of high levels of nuclear BAG-1 expression, through either BAG-1L or nuclear localised BAG-1S, caused resistance to γ -radiation induced apoptosis. This is the first study to demonstrate that nuclear BAG-1 inhibits the induction of apoptosis in colorectal adenomaderived cells, and suggests that nuclear localised BAG-1 expression may confer a survival advantage on adenoma cells in vivo, which could be important in the early stages of colorectal carcinogenesis.…”

Section: Discussionmentioning

confidence: 95%

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

Barnes¹,

Arhel²,

Ss³

et al. 2005

Apoptosis

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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, 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 gamma-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 gamma-radiation or exposure to EB1089. Furthermore the expression of cytoplasmic BAG-1S isoform fused with a nuclear localisation signal protected against gamma-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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Section: Discussionmentioning

confidence: 95%

“…Recently it has been reported that nuclear BAG-1 expression reflects poorer prognosis and is potentially a useful predictive factor for distant metastasis in patients suffering from colorectal cancer. 24 This suggests that nuclear BAG-1L could be important in the development of colorectal cancer.…”

Section: Introductionmentioning

confidence: 98%

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

Barnes¹,

Arhel²,

Ss³

et al. 2005

Apoptosis

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“…The percentage of CRC cases exhibiting nuclear BAG-1 positivity was significantly higher in distant metastasis-positive cases than in distant metastasis-negative cases, overall survival was significantly shorter for patients with tumors exhibiting BAG-1 positive nuclei than those without nuclear BAG-1-staining, and indicated that nuclear BAG-1 expression was the only independent prognostic variable for mortality (Kikuchi et al, 2002).…”

Section: Relationship Between St13 Expression and Survivalmentioning

confidence: 88%

Evaluation of ST13 gene expression in colorectal cancer patients

Dong

Zheng

et al. 2005

J. Zhejiang Univ. - Sci. B

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Abstract:We identified a novel gene ST13 from a subtractive cDNA library of normal intestinal mucosa in 1993, more studies showed that ST13 was a co-chaperone of Hsp70s. Recently we detected the ST13 gene expression in tumor tissue and adjacent normal tissue of the same colorectal cancer patient and investigated if the ST13 gene expression might have any prognostic value. Analysis was performed at molecular level by reverse transcription-PCR using real-time detection method. We measured two genes simultaneously, ST13 as the target gene and glyceraldehydes-3-phosphate dehydrogenase as a reference gene, in primary colorectal tumor specimens and tumor-adjacent normal mucosa specimens from 50 colorectal cancer patients. The expression levels of the ST13 gene were significantly decreased in primary tumors compared with adjacent mucosa (P<0.05). But there were no significant differences in the expression of ST13 as compared with different Dukes' stage, tumor differentiation grade, invasion depth, lymph node metastasis and disease-specific survival.

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“…Bag-1 almost has no expression in normal tissues, but in the breast, ovarian, oral cavity, bowel malignancy, prostate cancer and glioma has the positive express [1][2][3][4][5][6][7] . Liu et al [8] using fluorescence quantitative polymerase chain reaction (PCR) testing also found the lung cancer patients who have Bag-1 lower expression survived longer than those who have higher expression of expression of Bag-1, so Bag-1 high expression may be related to the poor outcome.…”

Section: Discussionmentioning

confidence: 99%