title: Overexpression of the retinoic acid-responsive gene Stra6 in human cancers and its synergistic induction by Wnt-1 and retinoic acid.
abstract: Genetic defects in the Wnt-1 signaling pathway contribute to human tumor progression and are especially prevalent in colorectal cancer. We screened mouse C57MG cells to isolate mRNAs induced by Wnt-1 and identified Stra6, an mRNA known to be up-regulated by retinoic acid. Up-regulation of Stra6 mRNA was also observed in hyperplastic mammary tissue and mammary gland tumors from transgenic mice expressing Wnt-1 and in human tumors that frequently harbor defects in Wnt-1 signaling. Stimulation of C57MG cells with retinoic acid plus Wnt-1 resulted in expression of Stra6 transcript to levels greatly exceeding that observed with either stimulus alone. This synergy could be explained in part by the up-regulation of retinoic acid receptor-gamma that was observed in response to Wnt-1 signaling. Accordingly, treatment of human colorectal cancer cell lines with retinoic acid resulted in the up-regulation of Stra6 mRNA and accumulation of Stra6 protein at the cell membrane. The data support a model in which Wnt-1 signaling synergizes with retinoids to activate retinoic acid receptor-gamma-responsive genes in human cancers.
authors.affiliation: Department of Molecular Oncology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: W
authors.initials: W
authors.lastname: Szeto
authors.forename: W
authors.initials: W
authors.lastname: Jiang
authors.forename: D A
authors.initials: DA
authors.lastname: Tice
authors.forename: B
authors.initials: B
authors.lastname: Rubinfeld
authors.forename: P G
authors.initials: PG
authors.lastname: Hollingshead
authors.forename: S E
authors.initials: SE
authors.lastname: Fong
authors.forename: D L
authors.initials: DL
authors.lastname: Dugger
authors.forename: T
authors.initials: T
authors.lastname: Pham
authors.forename: D G
authors.initials: DG
authors.lastname: Yansura
authors.forename: T A
authors.initials: TA
authors.lastname: Wong
authors.forename: J C
authors.initials: JC
authors.lastname: Grimaldi
authors.forename: R T
authors.initials: RT
authors.lastname: Corpuz
authors.forename: J S
authors.initials: JS
authors.lastname: Singh
authors.forename: G D
authors.initials: GD
authors.lastname: Frantz
authors.forename: B
authors.initials: B
authors.lastname: Devaux
authors.forename: C W
authors.initials: CW
authors.lastname: Crowley
authors.forename: R H
authors.initials: RH
authors.lastname: Schwall
authors.forename: D A
authors.initials: DA
authors.lastname: Eberhard
authors.forename: L
authors.initials: L
authors.lastname: Rastelli
authors.forename: P
authors.initials: P
authors.lastname: Polakis
authors.forename: D
authors.initials: D
authors.lastname: Pennica
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002884:Chromosomes, Human, Pair 15; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics / Q000302:isolation & purification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
chemical_list: D000970:Antineoplastic Agents; D018076:DNA, Complementary; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C108001:Stra6 protein, mouse; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; D014212:Tretinoin