Expression and subcellular localization of AT motif binding factor 1 in colon tumours

Kataoka,Hiromi; Miura,Yutaka; Kawaguchi,Makoto; Suzuki,Shugo; Okamoto,Yasuyuki; Ozeki,Keiji; Shimura,Takaya; Mizoshita,Tsutomu; Kubota,Eiji; Tanida,Satoshi; Takahashi,Satoru; Asai,Kiyofumi; Joh,Takashi

doi:10.3892/mmr.2017.7016

Expression and subcellular localization of AT motif binding factor 1 in colon tumours

Authors:
- Hiromi Kataoka
- Yutaka Miura
- Makoto Kawaguchi
- Shugo Suzuki
- Yasuyuki Okamoto
- Keiji Ozeki
- Takaya Shimura
- Tsutomu Mizoshita
- Eiji Kubota
- Satoshi Tanida
- Satoru Takahashi
- Kiyofumi Asai
- Takashi Joh
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Affiliations: Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan, Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan, Department of Pathology, Niigata Rosai Hospital, Japan Labor Health and Welfare Organization, Joetsu, Niigata 942‑8502, Japan, Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467‑8601, Japan
Published online on: July 15, 2017 https://doi.org/10.3892/mmr.2017.7016
Pages: 3095-3102
Copyright: © Kataoka et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

AT motif binding factor 1 (ATBF1) is a transcriptional regulator that functions as a tumour suppressor to negatively affect cancer cell growth. In the present study four specific polyclonal antibodies against ATBF1 were generated, and the expression and intracellular localization of ATBF1 in colonic mucosae, polyps, adenoma and adenocarcinoma tissue samples were investigated. The four polyclonal antibodies produced were as follows: MB34 and MB49, which recognize the N‑ and C‑terminal fragments of ATBF1, respectively; and D1‑120 and MB44, which recognize the middle fragments of ATBF1 that contain three nuclear localization signals (NLS). In total, 191 colon samples were examined by immunohistochemical analysis. In addition, colon cancer cells were transfected with four ATBF1 expression vectors, and the subcellular localization of each fragment was examined. Normal colon mucosal cells were not observed to express ATBF1. However, a small number of hyperplastic polyps, serrated adenomas and tubular adenomas expressed ATBF1. Colon cancer cells were observed to express D1‑120‑ and MB44‑reactive middle fragments of ATBF1 in their cell nuclei. However, the N‑ and C‑terminal fragments of ATBF1 did not translocate to the nucleus. Transfection of ATBF1 fragments revealed cleavage of the ATBF1 protein and nuclear translocation of the cleaved middle portion containing the NLS. A positive correlation between the cytoplasmic localization of the N‑ and C‑termini of ATBF1, nuclear localization of the middle portion of ATBF1 and malignant cancer cell invasion was observed. In conclusion, the results of the present study suggest that alterations in the expression and subcellular localization of ATBF1, as a result of post‑transcriptional modifications, are associated with malignant features of colon tumours.

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