title: Lewis Y regulates signaling molecules of the transforming growth factor             β pathway in ovarian carcinoma-derived RMG-I cells.
abstract: LeY (Lewis Y) is a difucosylated oligosaccharide carried by glycoconjugates             on the cell surface. Elevation of LeY is frequently observed in epithelial-derived             cancers and is correlated to pathological staging and prognosis. To study the             role of LeY on cancer cells, a stably LeY-overexpressing cell line, RMG-I-H, was             developed previously by transfection of the α1,2-fucosyltransferase gene, a key             enzyme that catalyzes the synthesis of LeY, into ovarian carcinoma-derived RMG-I             cells. Our studies have shown that LeY is involved in the changes in biological             behavior of RMG-I-H cells. However, the mechanism is still largely unknown. In             this study, we determined the structural relationship and co-localization between             LeY and TβRI/TβRII, respectively, and the potential cellular signaling mechanism             was also investigated. We found that both TβRI and TβRII contain the LeY structure,             and the level of LeY in TβRI and TβRII in RMG-I-H cells was significantly increased.             Overexpression of LeY up-regulates the phosphorylation of ERK, Akt and down-regulates             the phosphorylation of Smad2/3. In addition, the phosphorylation intensity was             attenuated significantly by LeY monoantibody. These findings suggest that LeY             is involved in the changes in biological behavior through TGF‑β receptors via             Smad, ERK/MAPK and PI3K/Akt signaling pathways. We suggest that LeY may be an             important composition of growth factor receptors and could be an attractive candidate             for cancer diagnosis and treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, PR China.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Li
authors.forename: Juan-Juan
authors.initials: JJ
authors.lastname: Liu
authors.forename: Da-Wo
authors.initials: DW
authors.lastname: Liu
authors.forename: Bei
authors.initials: B
authors.lastname: Lin
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Hao
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Cong
authors.forename: Lian-Cheng
authors.initials: LC
authors.lastname: Zhu
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Shu-Lan
authors.initials: SL
authors.lastname: Zhang
authors.forename: Masao
authors.initials: M
authors.lastname: Iwamori
mesh_terms: D000818:Animals; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*
chemical_list: D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D016212:Transforming Growth Factor beta