Role of p170 in lung tumorigenesis

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DESCRIPTION (provided by applicant): Gene expression can be regulated at both the transcriptional and translational level. Most of the translational regulation occurs at the level of translation initiation. Unlike transcription factors, eukaryotic translation Initiation Factors (eIF) have not been well recognized for their role in controlling cell growth. Recent studies suggest that elF4E, eIF2, and the p48 subunit of eIF3 may be involved in cell-growth control and oncogenesis. More recently, the expression of the putative subunit p170 of eIF3 was found to be up regulated in human lung, breast, cervical, and esophageal cancers. We have observed that p170 may be an important regulator for the expression of ribonucleotide reductase M2. Thus, eIF3 p170 may be an important regulator for controlling the expression of cell growth regulatory proteins and, thus, cell growth. The long-term goal of this project is to establish the role of eIF3 p170 in cell growth control and its relationship to human cancer. The hypothesis to be tested is that p170 is a major player in regulating the synthesis of specific cell growth control proteins. To this end, we plan to accomplish the following specific aims within the funding period: (1) to determine whether over-expression of pl70 causes tumorigenesis; (2) to determine whether p 170 regulates cell growth by controlling the synthesis of DNA synthesis enzymes such as ribonucleotide reductase M2; and (3) to study the regulation of eIF3 p170 expression. The role of a putative housekeeping protein, p170, in tumorigenesis has not been suggested previously and thus this study is novel. The information and probes obtained from this study will help us understand the molecular mechanism of translational control of cell growth. This work will certainly add to our understanding of the functional mechanism of translation initiation of protein synthesis.