Projects » Gunhild Sommer, PhD
The Role of the RNA Binding Protein La in Oral Tumor Biology (Start date 8/1/08)
Overview
We wish to establish the role of aberrant expressed RNA binding protein La in oral cancer pathogenesis.
Abstract
The cellular protein cyclin D1 stimulates the cell cycle, regulates transcriptional activity and cell mobility and invasion. In oral cancer cyclin D1 is misregulated and its overexpression contributes to the cancer development and progression. 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 cells) and elevated La protein levels strongly correlate with increased cyclin D1 protein levels in different cancer cell lines and patients samples tested. By dissecting the underlying regulatory mechanism, we have demonstrated that the La protein stimulates cyclin D1 mRNA translation by binding to the La response element (LaRE) located within the open reading frame of the cyclin D1 mRNA. 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 originated from oral cavity. In addition we will evaluate the oncogenic potential of the La protein in oral squamous cells. Hence, we will define whether overexpression of the La protein contributes to immortalization and in vitro transformation of oral squamous cells. These studies may help to understand oral cancer pathogenesis and might reveal novel therapeutic approaches, which is of immense importance for treatment of oral cancer.