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- Title
RCP is a human breast cancer-promoting gene with Ras-activating function.
- Authors
Jinqiu Zhang; Xuejing Liu; Datta, Arpita; Govindarajan, Kunde; Wai Leong Tam; Jianyong Han; George, Joshy; Wong, Christopher; Ramnarayanan, Kalpana; Tze Yoong Phua; Wan Yee Leong; Yang Sun Chan; Palanisamy, Nallasivam; Liu, Edison Tak-Bun; Karuturi, Krishna Murthy; Bing Lim; Miller, Lance David; Zhang, Jinqiu; Liu, Xuejing; Tam, Wai Leong
- 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.
- Subjects
BREAST cancer; EPITHELIAL cells; GENE expression; G proteins; CARCINOGENESIS; CELL lines; ANIMAL experimentation; BREAST tumors; CARRIER proteins; COMPARATIVE studies; GENES; IMMUNOHISTOCHEMISTRY; RESEARCH methodology; MEDICAL cooperation; MEMBRANE proteins; MICE; ONCOGENES; PHOSPHORYLATION; PROTEINS; RESEARCH; RESEARCH funding; TRANSFERASES; BIOINFORMATICS; EVALUATION research; GENE expression profiling; NEOPLASTIC cell transformation; GENOTYPES; CHEMICAL inhibitors
- Publication
Journal of Clinical Investigation, 2009, Vol 119, Issue 8, p2171
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI37622