Browsing by Subject "preneoplastic"

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    Mechanistic insight into the clonal expansion advantage of quiescent preneoplastic breast cells
    (2018-05) Masoud, Zahra
    Breast cancer, along with most cancers, is preceded by a precancerous state. The majority of cancer research is focused on understanding and targeting cells once they have reached the neoplastic stage. Advancements in early detection have identified the presence of preneoplastic lesions in the breast reporting that cells in these lesions remain phenotypically normal but have pro-growth genetic alterations. These emerging preneoplastic cells carry oncogenic drivers are significantly predisposed to developing tumors, but can stay in a latent state resembling normal quiescent cells in premalignant tissues. Expansion of such preneoplastic populations underlies a key cellular process driving premalignant development and is a hallmark in precancerous lesions and premalignant tissue fields surrounding tumors of epithelial origins such as the breast. Despite the indolent nature, preneoplastic clonal expansion is crucial to propagating and facilitating the accumulation of oncogenic alterations that drive clonal evolution of tumorigenesis and ultimately leads to neoplastic progression. The cellular controls of preneoplastic clonal expansion during premalignant development remain largely unknown. A major barrier to investigating preneoplastic clonal expansion is the lack of experimental models to recapitulate quiescent preneoplastic cells in premalignant tissues. Throughout my PhD research, I have devised a three-dimensional organoid model of quiescent preneoplastic breast cells. Using this model system, I have found that breast cells with aberrant AKT activation have distinct molecular controls that contribute to an altered homeostatic state of quiescence. This altered state underlies the maintenance of growth-arrest under normal conditions and the proliferative advantage in suppressive tissue environments.