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Current Topics in Biochemical Research   Volumes    Volume 12  Issue 1
Abstract
The eukaryotic initiation factor 3 and cancer
Renyuan Zhou, Alex Shen, Jiaqi Shi
Pages: 9 - 15
Number of pages: 7
Current Topics in Biochemical Research
Volume 12  Issue 1

Copyright © 2010 Research Trends. All rights reserved

ABSTRACT
 
Deregulated translation plays an important role in human cancer. Translation initiation factor eIF3 plays a central role in translation. Mammalian eIF3 is the largest of the initiation factors and exists as a protein complex with at least 13 non-identical subunits (eIF3a-m). The functions of the individual subunits have not yet been fully defined in mammals. It was suggested that mammalian eIF3 may consist of an active core of five subunits (eIF3a, b, c, g, i), with the remaining subunits serving to modulate eIF3 activity. Altering the expression level or the function of eIF3 may influence the synthesis of some proteins and consequently cause abnormal cell growth and malignant transformation. Seven eIF3 subunits have been implicated in human cancers. Our group has demonstrated reduced expression and loss of heterozygosity (LOH) of eIF3f in pancreatic cancer and melanoma. Recent studies also indicated that individual overexpression of 5 subunits of eIF3 promotes malignant transformation of NIH3T3 cells. eIF3a has been found to be overexpressed in breast, cervix, esophagus and lung cancer. eIF3b is significantly up-regulated in breast cancer. eIF3c is also found overexpressed in testicular seminomas. eIF3h was amplified and overexpressed in breast cancer and prostate cancer cell lines. Integration of MMTV into eIF3e/Int6 gene has been detected in breast cancers. Interestingly, reduced expression and LOH of eIF3e was recently found in human breast and lung cancers. Reduced eIF3e may increase eIF3 activity and protein synthesis. Therefore, deregulation of eIF3 subunits can contribute to tumorigenesis via induction of protein synthesis.
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