Elevated levels of eukaryotic translation initiation factor eIF-4E, mRNA in a broad spectrum of transformed cell lines

Miyagi, Yohei; Sugiyama, Akinori; Asai, Akio; Okazaki, Toshio; Kuchino, Yoshiyuki; Kerr, Sylvia J.

doi:10.1016/0304-3835(95)03737-h

Cited by 58 publications

(39 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, a recent investigation of a panel of cell lines showed that only transformed or stressed cells express the CUGinitiated forms of FGF-2 (Vagner et al, 1996). Since eIF4E is elevated in many transformed cells (Miyagi et al, 1995;Anthony et al, 1996) we speculate that eIF4E directly causes synthesis of the CUG-initiated FGF-2 isoforms in carcinomas. As such, eIF4E should be regarded as a general and important factor in tumor RT-FLANK LF-FLANK Figure 5 Sponge vascularization assays.…”

Section: Discussionmentioning

confidence: 70%

Elevated expression of eIF4E and FGF-2 isoforms during vascularization of breast carcinomas

et al. 1997

View full text Add to dashboard Cite

The translation initiation factor eIF4E is a novel protooncogene found over expressed in most breast carcinomas (Kerekatte et al., 1995), but the pathology where this elevation is initially manifested and its possible role in cancer progression are unknown. We report that eIF4E is markedly increased in vascularized malignant ductules of invasive carcinomas, whereas necrotic and avascular ductal carcinomas in situ display signi®cantly lower levels. eIF4E facilitates the synthesis of FGF-2, a powerful tumor angiogenic factor. Conversely, reducing eIF4E with antisense RNA in MDA-435 cells suppresses their tumorigenic and angiogenic properties, consistent with loss of FGF-2 synthesis. These ®ndings suggest a causal role for eIF4E in tumor vascularization.

show abstract

Section: Discussionmentioning

confidence: 70%

Elevated expression of eIF4E and FGF-2 isoforms during vascularization of breast carcinomas

et al. 1997

View full text Add to dashboard Cite

show abstract

“…Thus, failure to down-regulate eIF4E may result in loss of growth control. It is noteworthy that overexpression of eIF4E mRNA or protein has been observed in a wide variety of transformed cell lines and solid tumors [6].…”

Section: Introductionmentioning

confidence: 99%

Malignant transformation by the eukaryotic translation initiation factor 3 subunit p48 (eIF3e)

Mayeur

Hershey

2002

FEBS Letters

View full text Add to dashboard Cite

Several components of translation, e.g. eIF4E and PKR, are implicated in cancer. The e-subunit (p48) of mammalian initiation factor 3 is encoded by the Int6 gene, a common site for integration of the mouse mammary tumor virus genome, leading to the production of a truncated eukaryotic initiation factor-3e (eIF3e). Stable expression of a truncated eIF3e in NIH 3T3 cells causes malignant transformation by four criteria: foci formation; anchorage independent growth; accelerated growth; and lack of contact inhibition. Stable expression of full-length eIF3e does not cause transformation. The truncated eIF3e also inhibits the onset of apoptosis caused by serum starvation. ß

show abstract

“…(Note, however, that the level of eIF4G also falls dramatically when eIF4E is depleted (De Benedetti et al, 1991) so it is not possible to say which factor is the more important in bringing about these phenotypic consequences). High levels of expression of eIF4E and, in some cases, of eIF4G have been found in a variety of malignant human tumours (Miyagi et al, 1995;Li et al, 1997;Nathan et al, 1997a,b;Brass et al, 1997), but it is not known whether this is due to enhanced synthesis or a slower rate of degradation of these initiation factors. Elevated levels of mRNA for eIF4E are seen in cells transformed with the oncogene c-myc (Rosenwald et al, 1993), as well as in normal T lymphocytes after activation by mitogens (Mao et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

1998

View full text Add to dashboard Cite

We have investigated the e ect of inducing apoptosis in BJAB and Jurkat cells on the cellular content of several polypeptide chain initiation factors. Serum deprivation results in inhibition of protein synthesis and induction of apoptosis in BJAB cells; at early times, there is selective degradation of polypeptide initiation factor eIF4G but no major losses of other key initiation factors. The disappearance of full length eIF4G is accompanied by the appearance of smaller forms of the protein, including a major product of approximately 76 kDa. Apoptosis induced by cycloheximide results in similar e ects. Both total cytoplasmic eIF4G and eIF4G associated with eIF4E are degraded with a half-life of 2 ± 4 h under these conditions. Treatment of serum-starved or cycloheximide-treated cells with Z-VAD.FMK or Z-DEVD.FMK, which inhibit caspases required for apoptosis, protects eIF4G from degradation and blocks the appearance of the ca. 76 kDa product. Exposure of BJAB cells to rapamycin rapidly inhibits protein synthesis but does not lead to acute degradation of eIF4G. In both BJAB and Jurkat cells induction of apoptosis with anti-Fas antibody or etoposide also results in the selective loss of eIF4G, which is inhibitable by Z-VAD.FMK. These data suggest that eIF4G is selectively targeted for cleavage as cells undergo apoptosis and is a substrate for proteases activated during this process.

show abstract

Elevated levels of eukaryotic translation initiation factor eIF-4E, mRNA in a broad spectrum of transformed cell lines

Cited by 58 publications

References 17 publications

Elevated expression of eIF4E and FGF-2 isoforms during vascularization of breast carcinomas

Elevated expression of eIF4E and FGF-2 isoforms during vascularization of breast carcinomas

Malignant transformation by the eukaryotic translation initiation factor 3 subunit p48 (eIF3e)

Degradation of eukaryotic polypeptide chain initiation factor (eIF) 4G in response to induction of apoptosis in human lymphoma cell lines

Contact Info

Product

Resources

About