Gene Expression Profiling in the Developing Mammary Gland
Creators: name: University Of California Office Of The President
Publisher: name: University of California Office of the President
publisherIdentifier: https://ror.org/00dmfq477
publisherIdentifierScheme: ROR
Year: 2024

description: Cancer is a complex, dynamic process in which a tumor cell must communicate with the cells of its host in order to grow and progress. By studying how the normal mammary gland cells communicate with their environment and develop into a normal structure, we can find clues as to how this communication is miswired in breast cancer. Such aberrant signaling could provide novel targets for drug discovery efforts and may also explain risk factors of breast cancer such as early menarche and late pregnancy. Recent advances in genomics technologies and computing are giving researchers more power to study cellular communication on the genome scale. We propose to apply these technologies to study the signaling machinery that a mammary gland uses to develop into a functioning organ. Specifically, we would like to find the signals that direct the mammary ducts to invade its environment and subsequently branch into a tree. These processes are necessary for maturation of the organ and a defect in such processes may lead to breast cancer formation.
 
 
 
 
 
 
 
 The central question of the proposal is to find the messages that normal mammary ductal cells use to remodel their environment and grow into a ductal tree. Importantly, we would like to understand the communications that non-ductal cells make with the developing tree and how such "stromal" cells guide the development of the mammary gland. We ask how these messages compare in different portions of the mammary gland, such as in the invading edges of the tree compared to branch points in the existing tree. We also ask how these messages are altered throughout the estrus cycle of the host. Our proposed work enables us to read these messages in a complete and unbiased fashion.
 
 
 
 
 
 
 
 In order to more easily work with the mammary gland, we utilize transgenic mice in which a fluorescent protein has been placed into the genome of mice. These mice have fluorescently green mammary glands that can be easily visualized for surgical purposes. In this way, we can dissect different portions of the mammary gland and then isolate the chemical messages, or RNA, that direct cell communication and other processes. These chemical messages can be "read" through the use of microarrays, or glass slides that contain thousands of DNA spots, each of which is specific for a unique gene. These microarrays can reveal which of the many thousands of genes are activated in a given tissue. In this way, we can read the complete chemical message of the developing mammary gland in an unbiased fashion. Furthermore, by creating transgenic mice that lack a specific gene, we can reveal the normal function of a gene by asking how its absence alters the expression profile of the tissue.
 
 
 
 
 
 
 
 We utilize a completely novel to approach to address our research questions. First, we study the expression profiles of normal developing mammary gland tissue, rather than cell lines or cultured mammary organs. We also utilize a novel surgical approach to isolate different portions of the mammary gland for subsequent analysis. Furthermore, our analysis involves the use of DNA microarrays, a recent invention that can be used to address questions on the genomic scale. We use these microarrays to detect the thousand of genes that are activated in different portions of the duct during different stages of estrus. We also address how the patterns of gene activation are altered in transgenic mice which are engineered to lack a specific gene. The combined result of these approaches is a complete and unbiased analysis of the messages that govern the development of the normal mammary gland.