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Professor studies development of breast cancer

Dr. Maureen Dunbar, Associate Professor of Biology at Penn State Berks, spends much of her time in the lab studying the role of a particular protein, PTHrP (parathyroid hormone-related protein), and its association with normal development of the mammary gland, the organ present in mammals that produces milk for the young. Dunbar explains that by studying the effect of too much or too little PTHrP, a more complete understanding of the maturation of the mammary gland is possible. As the maturation process becomes clear, problems associated with PTHrP may help scientists better understand breast cancer.

"A perpetual misconception concerning scientific research involves the value of basic research," explains Dunbar. "Trying to understand the normal function of an organ propels much basic biological research yet this type of research may not seem as important as the work done trying to understand how to treat cancerous cells. Lack of fundamental understanding of normal cellular function can impede progress in treating a disease like cancer and is therefore quite important to ongoing efforts to treat cancer."

Dunbar further explains that cancer is a disease that results when cells lose their ability to regulate growth. Cancer cells will grow uncontrollably until they eventually destroy normal tissue causing an organ to stop functioning. In order to delineate the steps that a normal cell undergoes on its path to becoming a cancerous one requires detailed knowledge of normal cellular function in each particular organ. The cells in each organ are unique, which makes treating cancer a project that requires an understanding of each organ.
The mammary gland is actually a specialized sebaceous gland containing milk-producing structures called alveoli. The aveoli are embedded in a cushion of fat to help protect the gland. Each alveolus (the singular of aveoli) connects to a duct through which the milk flows until it is secreted through the nipple of the breast.

A mammal may have one or multiple (up to eleven pairs) of mammary glands, depending on the species. The glands in both sexes are premature until puberty when, under the influence of ovarian hormones, the glands begin to develop in females. During pregnancy the mammary ducts grow and develop further in preparation for producing milk for the young. The maturation of the mammary gland involves continual secretion of cellular signals helping to regulate that growth; PTHrP is one of those signals.

Two tissues involved in normal mammary gland development are the epithelial and mesenchymal with PTHrP serving a messenger between the two tissues to deliver information sent by estrogen. This small protein appears to function as a negative regulator of estrogen-induced growth during puberty.

"As part of collaboration with Yale University, my laboratory has been studying a genetically engineered mouse strain that overproduces PTHrP in the mammary glands," states Dunbar. "These mice have defects in mammary development during puberty that appear to be the result of abnormal estrogen signaling in the mammary gland. Experiments are currently ongoing to unravel the mechanisms by which PTHrP may regulate estrogen-induced growth of the mammary gland.

"Many published results have implicated estrogen as a potential carcinogen for breast tissue, so the interaction of PTHrP with estrogen in the mammary glands could lead to a better understanding of how this tissue becomes cancerous. Recent findings in breast cancer research have indicated that a woman's risk for breast cancer increases the longer she delays childbirth. This increased risk appears to be due to the fact that the immature cells of the pre- or non-pregnant breast are more susceptible to the cancer-causing effects of estrogen. The fact that PTHrP appears to be involved at this critical stage of breast development could lead to a better understanding, and potential treatment, for breast cancer.
The role of PTHrP in mammary development can also be studied using a cell culture model. Undergraduate students at Penn State Berks have developed a cell culture system to study the effects of estrogen and PTHrP on mammary cell growth.  Using these cultured mammary cells, the students have identified several factors that may act in concert with PTHrP to regulate mammary cell growth.

"Findings from student research have been presented at national meetings and have been published in professional journals," states Dunbar. "The excitement that undergraduates exhibit when they generate a novel finding is one of the most gratifying aspects of my job. Students learn in a way that cannot be replicated in the classroom. They learn invaluable skills such as teamwork, communication, and confidence. The time I spend with students engaged in research is always time well spent.

"The research performed in my laboratory is aimed at better defining the role of PTHrP in normal mammary gland development. My hope is that this work will ultimately result in improved treatments for breast cancer, but for now I remain focused on the interaction of PTHrP within the epithelial and mesenchymal tissues. My students and I enjoy the small victories that result from basic research, as well as the camaraderie that results from working on a team toward a larger goal."

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