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Zonula Occludens-1 (ZO-1) Redistribution Is Involved in the Regulation of Cell Dissociation in Pancreatic Cancer Cells

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Abstract

In our previous study, dissociation factor (DF) and mitogen-activated protein kinase kinase 2 (MEK2) were isolated as factors relating to cancer cell dissociation in pancreatic cancer cells. On the other hand, tight junction protein zonula occludens 1 (ZO-1) has been indicated to be involved in carcinogenesis. In this study, the expression of ZO-1 and a downstream kinase of MEK2, extracellular signal-regulated kinase 2 (ERK2), was analyzed to clarify the regulatory mechanism of cell dissociation in pancreatic cancer cells. Two hamster (PC-1.0 and PC-1) and two human (AsPC-1 and CAPAN-2) pancreatic cancer cell lines were used. Immunocytochemical study was performed using anti-ZO-1, ERK2, and phosphorylated ERK1/2 (p-ERK1/2) antibodies. DF treatment obviously disrupted ZO-1 expression at the sites of cell–cell contact and markedly induced ERK2 and p-ERK1/2 expression, as well as the dissociation of cell clones in PC-1 and CAPAN-2 cells. In contrast, U0126 (a MEK1/2 inhibitor) treatment significantly induced the peripheral distribution of ZO-1 as well as cell aggregation in PC-1.0 and AsPC-1 cells, which usually grew as single cells, but seriously suppressed ERK2 and p-ERK1/2 expression. We conclude that redistribution of ZO-1 is closely correlated with cell dissociation status in pancreatic cancer cells through activation of ERK2.

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Authors and Affiliations

  1. Department of Surgery II, Kumamoto University Medical School, Honjo 1-1-1, Kumamoto, 860-8556, Japan

    Xiaodong Tan MD, Hiroshi Egami MD, PhD, Shinji Ishikawa MD, PhD, Takashi Kurizaki MD, PhD, Masahiko Hirota MD, PhD & Michio Ogawa MD, PhD

Authors
  1. Xiaodong Tan MD
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  2. Hiroshi Egami MD, PhD
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  3. Shinji Ishikawa MD, PhD
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  4. Takashi Kurizaki MD, PhD
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  5. Masahiko Hirota MD, PhD
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  6. Michio Ogawa MD, PhD
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Corresponding author

Correspondence to Hiroshi Egami MD, PhD.

Additional information

This work was supported by a grant in aid from the Ministry of Education, Culture, and Science of Japan.

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Tan, X., Egami, H., Ishikawa, S. et al. Zonula Occludens-1 (ZO-1) Redistribution Is Involved in the Regulation of Cell Dissociation in Pancreatic Cancer Cells. Dig Dis Sci 50, 1402–1409 (2005). https://doi.org/10.1007/s10620-005-2853-9

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  • DOI: https://doi.org/10.1007/s10620-005-2853-9

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