Overexpression of the proto‐oncogene/translation factor 4E in breast‐carcinoma cell lines

The expression of the proto‐oncogene, translation factor elF‐4E, was examined in breast‐cell lines: 5 carcinomas and 2 normal. At the protein level, elF‐4E was 10 times higher in the carcinoma lines than in normal cells, which is comparable to the level found in breast‐cancer biopsies. The elevation appears to be due to increased transcription, since the elF‐4E mRNA was correspondingly increased. These results demonstrate that cells isolated from naturally occurring breast carcinomas maintain an elevated expression of the factor. Turnover rates for elF‐4E (mRNA and protein) were determined for normal and cancer cells. We found that elF‐4E mRNA is relatively stable during an 8‐hr incubation with Actinomycin D, but the half‐life of the protein is fairly short (≈4.5 hr). This suggests that, in proliferating cells, elF‐4E may be turning over rapidly, possibly to fine‐tune the changes in translation rates which occur during the cell cycle. © 1996 Wiley‐Liss, Inc.

[1]  A. De Benedetti,et al.  Translational regulation of vascular permeability factor by eukaryotic initiation factor 4E: Implications for tumor angiogenesis , 1996, International journal of cancer.

[2]  C. Kevil,et al.  Translational enhancement of FGF-2 by eIF-4 factors, and alternate utilization of CUG and AUG codons for translation initiation. , 1995, Oncogene.

[3]  A. De Benedetti,et al.  The proto‐oncogene/translation factor eIF4E: A survey of its expression in breast carcinomas , 1995, International journal of cancer.

[4]  L. Shantz,et al.  Overproduction of ornithine decarboxylase caused by relief of translational repression is associated with neoplastic transformation. , 1994, Cancer research.

[5]  A. De Benedetti,et al.  Mechanism of differential regulation of IL-2 in murine Th1 and Th2 T cell subsets. 1. Induction of IL-2 transcription in Th2 cells by up-regulation of transcription factors with the protein synthesis initiation factor 4E. , 1994, Journal of immunology.

[6]  N. Sonenberg,et al.  Elevated levels of cyclin D1 protein in response to increased expression of eukaryotic initiation factor 4E , 1993, Molecular and cellular biology.

[7]  N. Sonenberg Translation factors as effectors of cell growth and tumorigenesis. , 1993, Current opinion in cell biology.

[8]  K. Isselbacher,et al.  Increased expression of eukaryotic translation initiation factors eIF-4E and eIF-2 alpha in response to growth induction by c-myc. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[9]  N. Sonenberg,et al.  Ras mediates translation initiation factor 4E-induced malignant transformation. , 1992, Genes & development.

[10]  R. Rhoads,et al.  Ras transformation of cloned rat embryo fibroblasts results in increased rates of protein synthesis and phosphorylation of eukaryotic initiation factor 4E. , 1992, The Journal of biological chemistry.

[11]  A. De Benedetti,et al.  Expression of antisense RNA against initiation factor eIF-4E mRNA in HeLa cells results in lengthened cell division times, diminished translation rates, and reduced levels of both eIF-4E and the p220 component of eIF-4F , 1991, Molecular and cellular biology.

[12]  W. Rychlik,et al.  Increased rate of phosphorylation-dephosphorylation of the translational initiation factor eIF-4E correlates with the induction of protein and glycoprotein biosynthesis in activated B lymphocytes. , 1990, The Journal of biological chemistry.

[13]  A. De Benedetti,et al.  Overexpression of eukaryotic protein synthesis initiation factor 4E in HeLa cells results in aberrant growth and morphology. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[14]  N. Sonenberg,et al.  Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap , 1990, Nature.

[15]  E. Harlow,et al.  Antibodies: A Laboratory Manual , 1988 .

[16]  M. Cole The myc oncogene: its role in transformation and differentiation. , 1986, Annual review of genetics.