Elongation factor-1 (EF-1) is a G protein and plays an important role in translation by mediating the transport of amino acyl tRNA to 80S ribosomes. It contains four major subunits, EF-1alpha, EF-1beta, EF-1c, and EF-1delta. We have demonstrated that human EF-1gamma hybridizing RNA was overexpressed in 25 of 29 colorectal carcinomas, 13 of 25 colorectal adenomas, and 7 out of 9 pancreatic adenocarcinomas. We determined that the nucleotide sequence of EF-1gamma RNA is altered in one colorectal carcinoma specimen, but not in normal appearing adjacent mucosa. We propose to: 1. determine if NIH3T3 cells and/or colon adenoma cell lines VACO 235 and VACO 330 undergo changes in growth properties associated with tumorigenic transformation when EF-1gamma is overexpressed following introduction of either the wild type EF-1gamma coding sequence or the altered coding sequence mentioned above using an expression vector; 2. determine if sequence variation in the EF-1gamma mRNA occurs in other colorectal tumors; 3. determine the gene copy number and chromosomal location for EF-1gamma; and 4. determine the nucleotide sequence in and around the gene(s). This characterization of the gene will allow us to determine if any variations we observe in EF-1gamma RNA are due to mutations in the EF-1gamma gene or are a result of expression of another EF-1gamma gene in tumors, that are not expressed in normal human colon. It will also provide an important part of the foundation for future studies on regulatory sequences of the gene that may play a role in the overexpression of this gene in colorectal cancer. The proposed studies will provide important information for understanding the potential role of EF-1gamma in tumorigenesis. The recent finding that constitutive expression of EF-1 alpha in cell lines makes them more susceptible to chemically and physically induced transformation makes our finding even more significant since EF-1gamma is believed to be a stimulator of guanosine nucleotide exchange by EF-1alpha.
| Frazier, M L; Inamdar, N; Alvula, S et al. (1998) Few point mutations in elongation factor-1gamma gene in gastrointestinal carcinoma. Mol Carcinog 22:9-15 |
| Mathur, S; Cleary, K R; Inamdar, N et al. (1998) Overexpression of elongation factor-1gamma protein in colorectal carcinoma. Cancer 82:816-21 |
| Jones Jr, D V; Wu, E; Manire, M et al. (1997) Cis-acting elements required for expression of the nonspecific cross-reacting antigen gene in colorectal carcinoma. Gastroenterology 112:776-82 |
| Jeon, H M; Lynch, P M; Howard, L et al. (1996) Mutation of the hMSH2 gene in two families with hereditary nonpolyposis colorectal cancer. Hum Mutat 7:327-33 |
