In research that could significantly advance the pace of drug discovery in the fight against breast cancer, Harvard Medical School investigators have announced in the Journal of Proteome Research that they have created the first publicly available library of reliably expressible proteins of a human disease, in this case for breast cancer.
Perhaps more significantly, these researchers expressed a subset of the 1,300 protein-expressing complementary DNAs in the library into a model system mimicking cells of a human breast, allowing them to study on a broad scale how these proteins might contribute to the development of breast cancer. Through this comprehensive approach, they identified potentially novel functional activities for both well known and lesser-known breast cancer-associated proteins.
"The process of carcinogenesis is complex and involves the activation of many different cellular programs," says Joan Brugge, PhD, Chair, HMS Department of Cell Biology, and co-principal investigator of this initiative, called Breast Cancer 1000. "A significant limitation for breast cancer research has been the inability to distinguish whether certain proteins that are altered in breast tumor cells are the cause or the effect of conversion of normal breast cells to malignancy. The systematic approach that we've enabled and demonstrated will allow researchers to track cancer-causing proteins in simulated environments, with the goal of learning how to impede them."
"The availability of this collection will enable pilot experimentation and accelerate the development of faster techniques for studying breast cancer in a mammalian setting," says Joshua LaBaer, MD, PhD, director of the Harvard Institute of Proteomics (a division of Harvard Medical School), and also co-principal investigator. "To advance breast cancer research quickly, we are making the BC1000 library publicly available. It can be viewed from the Harvard Institute of Proteomics website.
"Drug design teams in the pharmaceutical industry traditionally have not used proteomics approaches to screen for potential targets, primarily because systematic proteomic tools are in their infancy," said Steven Carr, PhD, who was not part of this research team, and who leads the Proteomics group at the Broad Institute (of Harvard University and Massachusetts Institute of Technology). "While this work is highly in-vitro and needs further validation, the tools and approaches demonstrated in this study show a potentially valuable screening tool for drug companies, primarily as a means to triage for novel targets to design drugs around," said Carr, who prior to joining the Broad was director of Computational and Structural Sciences at SmithKline Pharmaceuticals and (now GlaxoSmithKline) and led protein science and proteomics groups at Millennium Pharmaceuticals. "This study helps lay the groundwork for new and refined proteomics tools for cancer and other diseases."
The Breast Cancer 1000 library is a collection of complementary DNA (cDNA) associated with breast cancer. Complementary DNA is generated from mRNA, which is produced by genes and contains the instructions on how to produce proteins. However, mRNAs are unstable outside of a cell, and therefore scientists convert it to cDNA for further long-term use. Researchers in BC1000 created a sequence-validated collection of roughly 1,300 breast cancer-related cDNAs ranging from well-studied breast cancer-causing genes to less conspicuous breast cancer-associated cDNAs.
SOURCES:
Journal of Proteome Research, online edition, February 8, 2006
Harvard Institute of Proteomics (http://www.hip.harvard.edu)
Harvard Medical School (http://hms.harvard.edu)
