The National Cancer Institute estimates that nearly 13 percent (one in eight) of all women in the United States will develop breast cancer. It remains the most common malignancy among women in this country and, for those between the ages of 40 and 45, the most lethal. Each year more than 180,000 American women develop the disease, and each year nearly 50,000 die from it.

A cell's native microenvironment can play a vital role in the development of cancer. This image shows breast cells embedded in the extracellular matrix (ECM). The cells' nuclei (large blue spheres) and the ECM are constantly interacting, sending messages back and forth. When cells become malignant, this communication is disrupted.

Mina Bissell, an award-winning researcher in cell biology and the director of Berkeley Lab's Life Sciences Division, came to this country from her native Iran at the age of 18 to study chemistry. She received her doctorate from Harvard University, with a focus on bacterial genetics.

This atypical background for breast-cancer research took her off the beaten track: when most everyone else was searching for oncogenes, cancer-causing genes, Bissell was seeking a precise definition of the "normal" state of affairs in cells.

"The answers led me to doubt that a change in a single gene could cause cancer," she says. "It didn't make any sense to me."

Further studies led Bissell to identify a link between breast cancer and a network of fibrous and globular proteins that surround and support breast cells, called the "extracellular matrix" or ECM. Until Bissell's revelation, it had been thought that the ECM was a sort of inert scaffolding upon which cells grow and develop, with no obvious role in malignancy.

Bissell has since demonstrated that the ECM is a dynamic player in cell growth and development -- and in the spread of cancer and other aberrations as well. Her theory, once branded heretical, has now gained wide acceptance.

"Cancer is the result not just of genetic change, not just of loss of growth regulation, or of environmental factors or aging, but an interweaving of all of these factors," Bissell says.

"To understand the mechanisms involved in cancer induction, one has to understand the factors that allow the cells to retain their normal phenotype," she says. "Given that all cells have the same genetic information and almost all retain the ability to grow, what tells the cells (in their natural habitat) to stop growing? What allows them to retain form and function? What makes a liver cell a liver and a breast cell a breast?"

Bissell's research provides some promising cues for possible future therapies. Her research demonstrates that in some cases what is happening outside a cell can be as important as the presence of cancerous genes within. This points to the possibility that the disease may be treated or perhaps even prevented through means other than conventional genetic therapy.

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