The polo-like kinases (PLKs) are important proteins that are required for cells to divide normally. Abnormal levels of these proteins have been linked to the improper division of cells, a hallmark of cancer. In humans, the PLKs have been implicated in several different types of cancer including breast, liver, skin, and colorectal. To study the effects of one of these genes at a more functional level, we have developed a mouse model that is genetically modified and only has one copy of the PLK4 gene. This mouse develops several different types of cancers such as liver and lung cancer at a much higher rate than normal mice. Recently, we noticed that this mouse, as it ages, also displays both abnormal bone marrow and an enlarged spleen. We find an irregular distribution of cells and an abnormal level of key proteins that are important for normal cell function. These proteins are known to change in level or activity in blood cancers. Thus the abnormal bone marrow and enlarged spleen, along with the other molecular features that we have detected, suggests that this mouse has developed a type of blood cancer. Our preliminary data suggests that the mouse may be a model for a myeloid and/or lymphoproliferative neoplasia. Based on our initial observations, we will be conducting experiments using several techniques to look at cell division, protein levels, and other markers of these cancers. We will also be conducting research in human patient samples to determine if the level of PLK4 protein is altered and whether this is correlated with changes in other key markers of cancer. Through our research we hope to more accurately determine the role that the PLK4 protein as well as additional novel proteins may play in these blood cancers. Our findings will contribute towards a better
understanding of what goes wrong within cells that lead to the development of these disorders and whether PLK4 may be an important marker for early detection, an indicator of prognosis or potential targets for intervention for these cancers.
HOW THIS RESEARCH HELPS ADVANCE QUALITY CANCER CARE IN OUR COMMUNITY
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