Scientists Discover Genetic Pathway Responsible For Breast Cancer Cell Growth

"Wehave known for a very long time that estrogen causes the growth ofbreast cancer cells," says lead investigator Dr Vincent Giguère. "Thisis how oncologists came to use anti-estrogen as drugs to combat themost common forms of breast cancer." What has remained a mysteryhowever, is the molecular mechanism by which estrogen makes breastcancer cells grow. "Until this is solved, we will be no closer tofiguring out how to prevent and cure breast cancer," Dr Giguère noted.Over the past two decades researchers have identified around 20estrogen-activated genes that play a role in development of breastcancer. "That's about one gene discovery per year," says Dr Giguère."Using cutting edge new technology derived directly from the humangenome project, this study adds over hundred additional genes to thistotal."

The technology used information obtained from the humangenome project to create a new type of DNA microchip containing thepartial DNA sequences of approximately 19,000 genes. Dr Giguère's teamwas able to localize where the estrogen receptor was bound in thegenome of breast cancer cells, thereby identifying a large number ofgenes that respond to this hormone in a single experiment. "Thistechnology, first developed for the study of yeast, now offers theopportunity to rapidly identify, in a genome-wide manner, the genesinvolved in the response to natural hormones or drugs in normal andcancer cells," says co-author Dr François Robert from the IRCM.

Ofparticular importance was the discovery of a gene called FOXA1, knownas a transcription factor. "FOXA1 can be viewed as a facilitator ofestrogen action on cancer cells," says Josée Laganière, a graduatestudent at the MUHC and principal author of the paper. "It is found inbreast cancer tumours that express the estrogen receptor." In theirstudy, the researchers found that the FOXA1 gene was required for theestrogen receptor to activate the growth of breast cancer cells.

"Byinactivating the FOXA1 gene in laboratory cell cultures, we were ableto block the growth-inducing effect of estogen, and thus halt thegrowth of breast cancer cells," says Dr Giguère. In FOXA1 researchershave found a new target that affects the development of breast cancer.In practical terms, efforts can now be focused on developing a moreprecise cure/treatment for cancer based on this gene. "The problem withcancer drugs in general has been that they are often untargeted, whichis why patients experience side effects," notes Dr Giguère. "The morefocused the drugs the less side effects and the more chance you have tocure the disease."

"Research targeting individual moleculesassociated with pathogenesis of cancer has led to positive clinicalresults," says Dr Joseph Ragaz, Director of MUHC Oncology Program."Evidence-based data on agents such as Gleevac in leukemia, Avastin incolorectal cancer, and more recently with Herceptin for breast cancer,confirm that the efforts of researchers like Dr Giguere and his teamsave lives and money. These connections between research and healthcare are one of the strengths of academic hospitals like the MUHC."

TheResearch Institute of the McGill University Health Centre (RI MUHC) isa world-renowned biomedical and health-care hospital research centre.Located in Montreal, Quebec, the institute is the research arm of theMUHC, a university health center affiliated with the Faculty ofMedicine at McGill University. The institute supports over 500researchers, nearly 1000 graduate and post-doctoral students andoperates more than 300 laboratories devoted to a broad spectrum offundamental and clinical research. The Research Institute operates atthe forefront of knowledge, innovation and technology and isinextricably linked to the clinical programs of the MUHC, ensuring thatpatients benefit directly from the latest research-based knowledge. Forfurther details visit: www.muhc.ca/research.

The McGillUniversity Health Centre (MUHC) is a comprehensive academic healthinstitution with an international reputation for excellence in clinicalprograms, research and teaching. The MUHC is a merger of five teachinghospitals affiliated with the Faculty of Medicine at McGillUniversity--the Montreal Children's, Montreal General, Royal Victoria,and Montreal Neurological Hospitals, as well as the Montreal ChestInstitute. Building on the tradition of medical leadership of thefounding hospitals, the goal of the MUHC is to provide patient carebased on the most advanced knowledge in the health care field, and tocontribute to the development of new knowledge.