This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our preliminary data and published data show that the RNA-binding protein La is overexpressed in various types of cancer cells (including oropharyngeal squamous cell cancer SSC-25 cell line) and elevated La protein levels correlate with increased cyclin D1 protein levels in most of the cancer cell lines and patients samples tested. We hypothesize that overexpression of the cancer-associated RNA-binding protein La results in elevated cyclin D1 protein levels, which contributes to malignant transformation of oral squamous cells. To test this hypothesis we will determine the mRNA and protein expression levels of La and cyclin D1 in normal and tumor cells of oral/craniofacial origin. We also will evaluate the oncogenic potential of the La protein within oral squamous cells. . These studies may lead to the development of an oral squamous cell carcinoma model, which would be useful to understand key carcinogenic steps of a specific tumor and thereby provide novel starting points for therapeutic approaches. Hypothesis: We hypothesize that the oncogenic potential of aberrant elevated La protein contributes to cell proliferation, a hallmark of tumorigenesis in oral cancer.
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