Scientists discover genetic pathway responsible for breast cancer cell growth

August 09, 2005

MONTREAL 9 August 2005--Scientists at the MUHC have made an important discovery that will advance our understanding of how the female hormone estrogen causes growth of breast cancer cells. The research, in collaboration with scientists at the Institut de Recherches Cliniques de Montreal (IRCM) identifies 153 genes that respond to estrogen and one in particular that can be used to halt the growth of breast cancer cells. The study, published in today's Proceedings of the National Academy of Sciences (PNAS), will focus future research for a breast cancer cure. "We have known for a very long time that estrogen causes the growth of breast cancer cells," says lead investigator Dr. Vincent Giguère. "This is how oncologists came to use anti-estrogen as drugs to combat the most common forms of breast cancer." What has remained a mystery however, is the molecular mechanism by which estrogen makes breast cancer cells grow. "Until this is solved, we will be no closer to figuring out how to prevent and cure breast cancer," Dr. Giguère noted.

Over the past two decades researchers have identified around 20 estrogen-activated genes that play a role in development of breast cancer. "That's about one gene discovery per year," says Dr. Giguère. "Using cutting edge new technology derived directly from the human genome project, this study adds over hundred additional genes to this total."

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

Of particular importance was the discovery of a gene called FOXA1, known as a transcription factor. "FOXA1 can be viewed as a facilitator of estrogen action on cancer cells," says Josée Laganière, a graduate student at the MUHC and principal author of the paper. "It is found in breast cancer tumours that express the estrogen receptor." In their study, the researchers found that the FOXA1 gene was required for the estrogen receptor to activate the growth of breast cancer cells.

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

"Research targeting individual molecules associated with pathogenesis of cancer has led to positive clinical results," says Dr. Joseph Ragaz, Director of MUHC Oncology Program. "Evidence-based data on agents such as Gleevac in leukemia, Avastin in colorectal cancer, and more recently with Herceptin for breast cancer, confirm that the efforts of researchers like Dr. Giguere and his team save lives and money. These connections between research and health care are one of the strengths of academic hospitals like the MUHC."
-end-
The Research Institute of the McGill University Health Centre (RI MUHC) is a world-renowned biomedical and health-care hospital research centre. Located in Montreal, Quebec, the institute is the research arm of the MUHC, a university health center affiliated with the Faculty of Medicine at McGill University. The institute supports over 500 researchers, nearly 1000 graduate and post-doctoral students and operates more than 300 laboratories devoted to a broad spectrum of fundamental and clinical research. The Research Institute operates at the forefront of knowledge, innovation and technology and is inextricably linked to the clinical programs of the MUHC, ensuring that patients benefit directly from the latest research-based knowledge. For further details visit: www.muhc.ca/research.

The McGill University Health Centre (MUHC) is a comprehensive academic health institution with an international reputation for excellence in clinical programs, research and teaching. The MUHC is a merger of five teaching hospitals affiliated with the Faculty of Medicine at McGill University--the Montreal Children's, Montreal General, Royal Victoria, and Montreal Neurological Hospitals, as well as the Montreal Chest Institute. Building on the tradition of medical leadership of the founding hospitals, the goal of the MUHC is to provide patient care based on the most advanced knowledge in the health care field, and to contribute to the development of new knowledge.

McGill University

Related Breast Cancer Articles from Brightsurf:

Oncotarget: IGF2 expression in breast cancer tumors and in breast cancer cells
The Oncotarget authors propose that methylation of DVDMR represents a novel epigenetic biomarker that determines the levels of IGF2 protein expression in breast cancer.

Breast cancer: AI predicts which pre-malignant breast lesions will progress to advanced cancer
New research at Case Western Reserve University in Cleveland, Ohio, could help better determine which patients diagnosed with the pre-malignant breast cancer commonly as stage 0 are likely to progress to invasive breast cancer and therefore might benefit from additional therapy over and above surgery alone.

Partial breast irradiation effective treatment option for low-risk breast cancer
Partial breast irradiation produces similar long-term survival rates and risk for recurrence compared with whole breast irradiation for many women with low-risk, early stage breast cancer, according to new clinical data from a national clinical trial involving researchers from The Ohio State University Comprehensive Cancer Center - Arthur G.

Breast screening linked to 60 per cent lower risk of breast cancer death in first 10 years
Women who take part in breast screening have a significantly greater benefit from treatments than those who are not screened, according to a study of more than 50,000 women.

More clues revealed in link between normal breast changes and invasive breast cancer
A research team, led by investigators from Georgetown Lombardi Comprehensive Cancer Center, details how a natural and dramatic process -- changes in mammary glands to accommodate breastfeeding -- uses a molecular process believed to contribute to survival of pre-malignant breast cells.

Breast tissue tumor suppressor PTEN: A potential Achilles heel for breast cancer cells
A highly collaborative team of researchers at the Medical University of South Carolina and Ohio State University report in Nature Communications that they have identified a novel pathway for connective tissue PTEN in breast cancer cell response to radiotherapy.

Computers equal radiologists in assessing breast density and associated breast cancer risk
Automated breast-density evaluation was just as accurate in predicting women's risk of breast cancer, found and not found by mammography, as subjective evaluation done by radiologists, in a study led by researchers at UC San Francisco and Mayo Clinic.

Blood test can effectively rule out breast cancer, regardless of breast density
A new study published in PLOS ONE demonstrates that Videssa® Breast, a multi-protein biomarker blood test for breast cancer, is unaffected by breast density and can reliably rule out breast cancer in women with both dense and non-dense breast tissue.

Study shows influence of surgeons on likelihood of removal of healthy breast after breast cancer dia
Attending surgeons can have a strong influence on whether a patient undergoes contralateral prophylactic mastectomy after a diagnosis of breast cancer, according to a study published by JAMA Surgery.

Young breast cancer patients undergoing breast conserving surgery see improved prognosis
A new analysis indicates that breast cancer prognoses have improved over time in young women treated with breast conserving surgery.

Read More: Breast Cancer News and Breast Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.