Age and Breast Cancer

Many kinds of cancer afflict older people (or animals) and rarely occur in younger individuals. This phenomenon clearly provides an important clue to how cancer gets started, but there are few good ideas about why it happens in this way. Breast cancer is among the most frequently occurring of the cancers of old age. My students and I are trying to figure out how aging alters the relationship among the various parts of the mammary gland, and how this alteration might encourage tumor growth. We isolate the several different cell types of glands of different ages, and observe how they interact with one another in tissue culture. Both mouse and human cells are used for these experiments. Three enthusiastic undergraduates are currently hard at work on this project. They have helped us to zero in on proteins called growth factors that are produced in surprisingly large amounts by some cells in the old gland and could contribute to the first steps that lead to tumor formation.

Angela House is studying a specific growth factor called "transforming growth factor beta." She has learned how to measure the amount of messenger RNA produced that codes for synthesis of this protein. (Not only is this message synthesized by connective-tissue cells of the older gland, but, interestingly, its amount is altered by treatment of these cells with the female hormone estrogen and related hormones.) Kyle Miller has studied another group of growth factors called the "epidermal growth factor family." He is focusing on cell-surface molecules, called receptors, that recognize the growth factors themselves and start the target cells' response to them. He is measuring the number of receptors in mammary cells of different ages treated with different hormones. Pat Friel is our growth expert, who looks at how the various cell types proliferate under specific circumstances.

Our discovery that growth factors are produced in the old mammary gland is exciting because these stimulatory proteins may provoke damaged cells to begin growing into tumors. Our current studies are aimed at learning how and why these proteins are being produced in older individuals at a time of life when they would not be expected in the mammary gland. In the near future, we will artificially alter the amounts of these growth factors in mammary glands of old mice, so we can directly measure whether or not they actually have any effect on the number of tumors that develop. This will be a direct test of the contribution of the growth factors to cancer formation. We hope in this way to gain new and useful understanding of the disease process.