Elevated expression of eIF4E and FGF-2 isoforms during vascularization of breast carcinomas.
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 significantly 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 findings suggest a causal role for eIF4E in tumor vascularization.
Nathan
C A
CO
Department of Biochemistry, LSU Medical Center, Shreveport, Louisiana, USA.
Carter
P
P
Liu
L
L
Li
B D
BD
Abreo
F
F
Tudor
A
A
Zimmer
S G
SG
De Benedetti
A
A
D000818:Animals; D001943:Breast Neoplasms / Q000098:blood supply* / Q000235:genetics / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000378:metabolism / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology; D002458:Cell Fractionation; D039561:Eukaryotic Initiation Factor-4E; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D007536:Isomerism; D051379:Mice; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010448:Peptide Initiation Factors / Q000096:biosynthesis* / Q000187:drug effects; D014176:Protein Biosynthesis; D016372:RNA, Antisense / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D012156:Reticulocytes; D014407:Tumor Cells, Cultured
D039561:Eukaryotic Initiation Factor-4E; D010448:Peptide Initiation Factors; D016372:RNA, Antisense; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2