Expression pattern of REIC/Dkk-3 in various cell types and the implications of the soluble form in prostatic acinar development.
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.
Innovation Center Okayama for Nanobio-Targeted Therapy, Okayama University, Okayama, Japan.
Kai
K
Zhang
Masami
M
Watanabe
Yuji
Y
Kashiwakura
Shun-Ai
SA
Li
Kohei
K
Edamura
Peng
P
Huang
Ken
K
Yamaguchi
Yasutomo
Y
Nasu
Yasuyuki
Y
Kobayashi
Masakiyo
M
Sakaguchi
Kazuhiko
K
Ochiai
Hiroshi
H
Yamada
Kohji
K
Takei
Hideo
H
Ueki
Nam-Ho
NH
Huh
Ming
M
Li
Haruki
H
Kaku
Yanqun
Y
Na
Hiromi
H
Kumon
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D002477:Cells / Q000378:metabolism*; D002478:Cells, Cultured; D018925:Chemokines; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis / Q000187:drug effects / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D011467:Prostate / Q000254:growth & development* / Q000378:metabolism; D012995:Solubility
D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D036341:Intercellular Signaling Peptides and Proteins