title: RCP is a human breast cancer-promoting gene with Ras-activating function.
abstract: Aggressive forms of cancer are often defined by recurrent chromosomal alterations, yet in most cases, the causal or contributing genetic components remain poorly understood. Here, we utilized microarray informatics to identify candidate oncogenes potentially contributing to aggressive breast cancer behavior. We identified the Rab-coupling protein RCP (also known as RAB11FIP1), which is located at a chromosomal region frequently amplified in breast cancer (8p11-12) as a potential candidate. Overexpression of RCP in MCF10A normal human mammary epithelial cells resulted in acquisition of tumorigenic properties such as loss of contact inhibition, growth-factor independence, and anchorage-independent growth. Conversely, knockdown of RCP in human breast cancer cell lines inhibited colony formation, invasion, and migration in vitro and markedly reduced tumor formation and metastasis in mouse xenograft models. Overexpression of RCP enhanced ERK phosphorylation and increased Ras activation in vitro. As these results indicate that RCP is a multifunctional gene frequently amplified in breast cancer that encodes a protein with Ras-activating function, we suggest it has potential importance as a therapeutic target. Furthermore, these studies provide new insight into the emerging role of the Rab family of small G proteins and their interacting partners in carcinogenesis.
authors.affiliation: Stem Cell and Developmental Biology Program, Genome Institute of Singapore, Singapore.
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Zhang
authors.forename: Xuejing
authors.initials: X
authors.lastname: Liu
authors.forename: Arpita
authors.initials: A
authors.lastname: Datta
authors.forename: Kunde
authors.initials: K
authors.lastname: Govindarajan
authors.forename: Wai Leong
authors.initials: WL
authors.lastname: Tam
authors.forename: Jianyong
authors.initials: J
authors.lastname: Han
authors.forename: Joshy
authors.initials: J
authors.lastname: George
authors.forename: Christopher
authors.initials: C
authors.lastname: Wong
authors.forename: Kalpana
authors.initials: K
authors.lastname: Ramnarayanan
authors.forename: Tze Yoong
authors.initials: TY
authors.lastname: Phua
authors.forename: Wan Yee
authors.initials: WY
authors.lastname: Leong
authors.forename: Yang Sun
authors.initials: YS
authors.lastname: Chan
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.forename: Edison Tak-Bun
authors.initials: ET
authors.lastname: Liu
authors.forename: Krishna Murthy
authors.initials: KM
authors.lastname: Karuturi
authors.forename: Bing
authors.initials: B
authors.lastname: Lim
authors.forename: Lance David
authors.initials: LD
authors.lastname: Miller
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001943:Breast Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D019295:Computational Biology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D018628:Gene Dosage; D020869:Gene Expression Profiling; D018734:Genes, erbB-2; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes; D010766:Phosphorylation; D034622:RNA Interference; D020691:rab GTP-Binding Proteins / Q000502:physiology; D000099193:rab11 GTP-Binding Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D048049:Extracellular Signal-Regulated MAP Kinases; D008565:Membrane Proteins; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C488966:RAB11FIP1 protein, human; C509763:Rab25 protein, human