1 Howard Hughes Medical Institute, Centre for Cancer Research,
and 2 Department of Biology, Massachusetts Institute of Technology,
77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA
3 Whitehead Institute/MIT Centre for Genome Research,
9 Cambridge Centre, Cambridge , Massachusetts 02142, USA
4 Dana-Farber Cancer Institute, 44 Binney Street, Boston,
Massachusetts 02115, USA
Correspondence:
Introduction:
Additional References:
Other Links:
Feedback:
Correspondence and requests for materials
should be addressed to R.O.H.
e-mail: rohynes@mit.edu
The most damaging change during cancer
progression is the switch from a locally growing tumour to a metastatic
killer. This switch is believed to involve numerous alterations that allow
tumour cells to complete the complex series of events needed for metastasis.
Relatively few genes have been implicated in these events. Here we use
an in vivo selection scheme to select highly metastatic melanoma
cells. By analysing these cells on DNA arrays, we define a pattern of gene
expression that correlates with progression to a metastatic phenotype.
In particular, we show enhanced expression of several genes involved in
extracellular matrix assembly and of a second set of genes that regulate,
either directly or indirectly, the actin-based cytoskeleton. One of these,
the small GTPase RhoC, enhances metastasis when overexpressed, whereas
a dominant-negative Rho inhibits metastasis. Analysis of the phenotype
of cells expressing dominant-negative Rho or RhoC indicates that RhoC is
important in tumour cell invasion. The genomic approach allows us to identify
families of genes involved in a process, not just single genes, and can
indicate which molecular and cellular events might be important in complex
biological processes such as metastasis.
Additional References:
1. "Oncogenes as Molecular Targets within Active Chromatin".
2. "Mated Models of Gene Regulation in Eukaryotes".