Expression pattern of REIC/Dkk-3 in various cell types and the implications of the soluble form in prostatic acinar development

Kai Zhang, Masami Watanabe, Yuji Kashiwakura, Shun Ai Li, Kohei Edamura, Peng Huang, Ken Yamaguchi, Yasutomo Nasu, Yasuyuki Kobayashi, Masakiyo Sakaguchi, Kazuhiko Ochiai, Hiroshi Yamada, Kohji Takei, Hideo Ueki, Nam Ho Huh, Ming Li, Haruki Kaku, Yanqun Na, Hiromi Kumon

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The tumor suppressor REIC/Dkk-3 is a secretory protein which was originally identified to be downregulated in human immortalized cells. In the present study, we investigated the expression pattern of REIC/Dkk-3 in various cell types to characterize its physiological functions. We first examined the expression level of REIC/Dkk-3 in a broad range of cancer cell types and confirmed that it was significantly downregulated in all of the cell types. We also examined the tissue distribution pattern in a variety of normal mouse organs. Ubiquitous REIC/Dkk-3 protein expression was observed in the organs. The expression was abundant in the liver, heart and brain tissue, but was absent in the spleen and peripheral blood mononuclear cells. The immunohistochemical analyses revealed that the subcellular localization of REIC/Dkk-3 had a punctate pattern around the nucleus, indicating its association with secretory vesicles. In cancer cells stably transfected with REIC/Dkk-3, the protein was predominantly localized to the endoplasmic reticulum (ER) under observation with confocal microscopy. Because REIC/ Dkk-3 was found to be abundantly expressed in the acinar epithelial cells of the mouse prostate, we analyzed the effects of recombinant REIC/Dkk-3 protein on the acinar morphogenesis of RWPE-1 cells, which are derived from human normal prostate epithelium. Statistically significant acinar growth was observed in the culture condition with 10 μg/ml REIC/Dkk-3 protein, implicating the soluble form in prostatic acinar development. Current results suggest that REIC/Dkk-3 may play a role in regulating the morphological process of normal tissue architecture through an autocrine and/or paracrine manner.

Original languageEnglish
Pages (from-to)1495-1501
Number of pages7
JournalInternational journal of oncology
Volume37
Issue number6
DOIs
Publication statusPublished - Dec 2010

Keywords

  • Acinar development
  • Prostate
  • REIC/Dkk-3
  • Subcellular localization
  • Tissue distribution

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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