Aggressive forms of cancer are often driven by the abnormal over-expression of cancer-promoting genes, also known as oncogenes.
Studies at the Genome Institute of Singapore (GIS), a research institute under the Agency for Science, Technology and Research (A*STAR) of Singapore, have identified a gene, known as RCP (or RAB11FIP1), that is frequently amplified and over-expressed in breast cancer and functionally contributes to aggressive breast cancer behaviour.
The research findings are published in the July 20th online issue of Journal of Clinical Investigation (JCI).
The GIS team, led by Lance Miller, Ph.D., and Bing Lim, Ph.D., initially discovered that RCP expression was positively correlated with cancer recurrence in a population of breast cancer patients. This suggested that RCP may be required by some tumours for growth and metastatic spread to other organs.
When the researchers over-expressed RCP in non-cancerous breast cells, they found that RCP promotes migration, or cellular movement, which is a precursor to the ability of tumours to invade neighbouring tissues.
However, breast cancer cells in which RCP is over-expressed take on a more aggressive behaviour, including faster proliferation, enhanced migration/invasion and anchorage-independent growth.
The researchers also found that when the gene is silenced in breast cancer cells, the ability of the cells to form tumours and metastasize to other organs is greatly diminished.
They also found that RCP can activate the potent oncogene, Ras, which is aberrantly activated by mutation in about 15% of all human cancers.
"One objective in my laboratory is to discover new oncogenes that drive breast cancer progression so that we can devise therapeutic strategies for shutting these genes down," said Dr. Miller, now at Wake Forest University School of Medicine in North Carolina. "The involvement of RCP in breast cancer progression may have significant clinical ramifications, and we are now working towards a better understanding of its mechanism of action."
The JCI article is titled, "RCP is a novel breast cancer promoting gene with Ras activating function."
Jinqiu Zhang1,5,9, Xuejing Liu2,9, Arpita Datta2, Kunde Govindarajan3, Wai Leong Tam1, Jianyong Han1, Joshy George3,6, Christopher Wong2, Kalpana Ramnarayanan2, Tze Yoong Phua2, Wan Yee Leong2, Yang Sun Chan2, Nallasivam Palanisamy2,7, Edison Tak-Bun Liu2, Krishna Murthy Karuturi3, Bing Lim1,4,10 and Lance David Miller2,8,10
1 Stem Cell and Developmental Biology, Genome Institute of Singapore, Singapore
2 Cancer Biology and Pharmacology, Genome Institute of Singapore, Singapore
3 Computational and Mathematical Biology, Genome Institute of Singapore, Singapore
4 Center for Life Sciences, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
5 Current address: Stem Cell Disease Models, Institute of Medical Biology, Singapore
6 Current address: Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
7 Current address: Michigan Center for Translational Pathology, Department of Pathology, University of Michigan, Ann Arbor, MI, USA
8 Current address: Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
9 These authors contributed equally to this work
10 Corresponding authors:
Dr. Lance Miller:
at Wake Forest University School of Medicine, Winston Salem, NC,
Dr. Bing Lim:
at Genome Institute of Singapore
Genome Institute of Singapore: www.gis.a-star.edu.sg
The Genome Institute of Singapore (GIS) is a member of the Agency for Science, Technology and Research (A*STAR). It is a national initiative with a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.
Agency for Science, Technology and Research (A*STAR): www.a-star.edu.sg
A*STAR is Singapore's lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, Physical Sciences and Engineering, with a particular focus on fields essential to Singapore's manufacturing industry and new growth industries. It oversees 22 research institutes, consortia and centres, and supports extramural research with the universities, hospital research centres and other local and international partners. At the heart of this knowledge intensive work is human capital. Top local and international scientific talent drive knowledge creation at A*STAR research institutes. The agency also sends scholars for undergraduate, graduate and post-doctoral training in the best universities, a reflection of the high priority A*STAR places on nurturing the next generation of scientific talent.