Functional analysis on EphB and ephrin-b expressing in gastric mucosaand their expression behavior in gastric ulcer and cancer EphBephrin-B EphBephrin-Bephrin-BEphB Gastric UnitEphB2 EphBephrin-BEphB/ephrin-B EphBRhoA EphBephrin-B EphB/ephrin-B Several EphB receptors and ephrin-bs were detected in the gastric mucosa of the adult rodent stomach by RT-PCR amplification. Immunostaining showed complementary expression patterns, with EphB receptors preferentially expressed in the deeper regions and ephrin-bs in the superficial regions of the gastric units. In a mouse ulcer model EphB2 expression was upregulated in the regenerating epithelium. EphB signaling in primary gastric epithelial cells promoted cell retraction and repulsion at least in part through RhoA activation. Based on these findings the author propose that the EphB-positive progeny of gastric stem cells migrates from the isthmus towards the bottom of the gastric glands due to repulsive signals arising from contact with ephrin-bs, which are preferentially expressed in the more superficial regions of the isthmus and gastric pits. In a rat gastric cancer model EphB2 and ephrin-b were co-localized in Ki67-positive proliferative cells forming aberrant gastric units and gastric cancer cells were simultaneously expressed EphB receptors and ephrin-b ligands. These findings suggest that simultaneous expressions of both EphB receptors and ephrin-b indicates an characteristic of gastric cancer cells. 2009 2010 2011
Eph ephrin Clevers ephrin-b EphB van de Wetering et al., Cell, 2002; Batle et al., Cell, 2002 EphB/ephrin-B (1) EphB ephrin-b (2) EphB ephrin-b (3) EphB ephrin-b EphB/ephrin-B (1) Balb/cICR F344Wistar (2)RT-PCR 710 AZ521KATO IIIMNK-7 SH-10-TC RT-PCR EphB B1~B4, B6 ephrin-bb1~b3 (3) EphB (4) H,K-ATPase Ki67 GS-II UEA-I ABC HRP ABC-DAB 2 EphB1EphB2EphB3EphB4ephrinB1 2 (5) Okabe Okabe et al., 1971 Robert Robert et al., 1979 Hirose MNNG Hirose et al., 1989 (6) Dibona Dibona et al., 1979 (7) Time-Lapse Ephrin-B1-Fc/EphB2-Fc Time-Lapse RhoA Y27632 Ephrin-B1-FcEphB2-Fc (8) Ephrin-B1-Fc/EphB2-Fc vinculin phalloidin (9)RhoARac1 RhoARac1 (1)EphB/ephrin-B mrna RT-PCR RT-PCR EphB ephrin-b 1 EphB1 ephrin-b3 RT-PCR 10 EphB2 4 AZ521, KATOIII, MNK7, SH-10-TC EphB ephrin-b EphB2 EphB3 EphB2-B4
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ephrin-b1 5 Gastric Unit 5-5 710 Gastric Unit EphB EphB/ephrin-B 6 Ki67 EphB ephrin-b (3) EphB/ephrin-B Time-Lapse EphB ephrin-b Time-Lapse ephrin-b1-fc 15 Ephrin-B1-Fc EphB2-Fc Film ephrin-b1-fc Film 7 EphB!7 EphB/ephrin-B"#$%&'() *+,-"./012345!6 "#$%&'EphB(ephrin-B)* 710 EphB2 Ki67 EphB3 Ephrin-A1 (4) EphB/ephrin-B RhoARac1 Vinculin phalloidin EphB EphB EphB Rho GTPase
EphB RhoARac1 RhoA Y27632 EphB Y27632 ephrin-b1-fc EphB ephrin-b1-fc Y27632 EphB RhoA Rac1 EphB RhoA Rac1 ephrin-b1-fc EphB 5 RhoA 8Rac1 EphB RhoA EphB/ephrinB!9 Gastric Unit"#$%&'()* EphB/ephrin-B+,-. (5) EphB/ephrin-B Gastric Unit EphB ephrin-b EphB ephrin-b EphB/ephrin-B EphB ephrin-b 9Gastric Unit EphB/ephrin-B Gastric Unit EphB/ephrin-B EphB ephrin-b Gastric Unit 5 EphB2 ephrin-b1 87 2012 Ogawa K, Takemoto N, Ishii M, Mueller I, Pasquale E B, Nakajima T. Complementary expression and repulsive signaling suggest that EphB receptors and ephrin-b ligands control cell positioning in the gastric epithelium. Histochem Cell Biol 136: 617-636, 2011. Ishii M, Nakajima T, Ogawa K. Complementary expression of EphB receptors and ephrin-b ligands in the pyloric and duodenal
epithelium of adult mice. Histochem Cell Biol 136: 345-356, 2011. EphB ephrin-b 85 (2): 74, 2010. EphB RhoA 84(2): 63, 2009. 7 Kazushige Ogawa, Yasutaka Igura, Yuta Hayashi, Noritaka Saeki, Maki Ishii and Takayuki Nakajima EphB2 and ephrin-b1 expression in the boundary between the glandular and nonglandular epithelium of the rodent stomach 14th International Congress on Histochemistry and Cytochemistry Aug 26-29, 2012 Kyoto, Japan (Kyoto International Conference Center) EphB2ephrin- B1 87 2011123 EphB2 ephrin-b1 152 2011 9 20 EphB ephrin-b 85 2009 11 28 Kazushige Ogawa, Natsuki Takemoto, Maki Ishii, Takayuki Nakajima EphB/ephrin-B may regulate cell positioning in the gastric epithelium 50 2009 9 27 EphB ephrin-b 148 2009 9 25 Eph ephrinephb/ephrin-b 147 2009 4 4 http://www.vet.osakafu-u.ac.jp/anat/anat.html OGAWA KAZUSHIGE 60231221 NAKAJIMA TAKAYUKI 30333644 ISHII MAKI 50415535 PASQUALE, ELENA Sanford-Burnham Medical Research Institute (La Jolla, USA)