Adenovirus 5 early region 1A does not induce expression of the ewing sarcoma fusion product EWS-FLI1 in breast and ovarian cancer cell lines.
The adenovirus 5 early region 1A (E1A) can function as a tumor suppressor gene and is being used in clinical trials as a therapeutic agent for advanced breast, ovarian, and head and neck cancer. Recently, there has been a dispute regarding whether transfection with the E1A gene can induce expression of the Ewing sarcoma oncogenic fusion transcript EWS-FLI1 (Sanchez-Prieto et al., Nat. Med., 5: 1076-1079, 1999; Melot and Delattre, Nat. Med., 5: 1331, 1999; Kovar et al., Cancer Res., 60: 1557-1560, 2000). In an effort to settle the controversy, we tested several stable E1A transfectants of cell lines MDA-MB-231, MCF-7, MDA-MB-435 (breast cancer), SKOV3-ipl (ovarian cancer), and PC-3 (prostate cancer), as well as parental and vector-transfected controls, HEK 293 cells, and RD-ES (Ewing sarcoma) cells, for the EWS-FLI1 fusion product. The EWS-FLI1 transcript could not be identified with reverse transcription-PCR in any of the 13 E1A-transfected cell lines analyzed. Furthermore, the EWS-FLI1 fusion protein could not be detected by Western blot analysis in E1A-transfected cell lines. These results suggest that E1A transfection does not necessarily lead to expression of the oncogenic EWS-FLI1 fusion transcript. Thus, the potential induction of this gene rearrangement by E1A gene therapy is unlikely to be clinically significant in the treatment of advanced malignant disease.
Meric
F
F
Department of Surgical Oncology The University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA.
Liao
Y
Y
Lee
W P
WP
Pollock
R E
RE
Hung
M C
MC
D017500:Adenovirus E1A Proteins / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D003001:Cloning, Molecular; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1; D012333:RNA, Messenger / Q000378:metabolism; D034802:RNA-Binding Protein EWS; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000096:biosynthesis*; D014162:Transfection; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D017500:Adenovirus E1A Proteins; C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D012333:RNA, Messenger; D034802:RNA-Binding Protein EWS; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors