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Antisense Epidermal Growth Factor Receptor Transfection Impairs the Proliferative Ability of Human Rhabdomyosarcoma Cells¹

Cancer Research Institute, University of Bologna, Viale Filopanii 22, I-40126 Bologna [C. D. G., L. L., F. F., G. N., C. G., I. R., P. N., P-L. L.]; I.S.T. Biotechnology Satellite Unit, Bologna [L. L., G. N.]; and Laboratory of Molecular Oncology, DIBIT H.S. Raffaele, Via Olgettina 60, I-20132 Milano [M. M., L. S.], Italy

Human rhabdomyosarcoma cells express membrane epidermal growth factor receptor (EGF-R), which could confer responsiveness to EGF and transforming growth factor- (TGF-) of autocrine or paracrine origin. To study the role played by this growth factor circuit in the proliferation and differentiation of myogenic noeplastic cells, human rhabdomyosarcoma EGF-R-expressing cells (RD/18 clone) have been transfected with a plasmid containing a fragment of the EGF-R cDNA in the antisense orientation. in vitro growth and differentiative ability were studied on six antisense-transfected clones (AS) in comparison to parental RD/18 cells and to cells transfected with the plasmid containing only the neomycin resistance gene (NEO). A reduced EGF-R membrane expression was found in AS clones by decreased immunofluorescence with an anti-EGF-R monoclonal antibody. All AS transfectants had a greatly impaired proliferative ability, even when cultured in fetal bovine serum-containing medium. Proliferation of AS clones was completely blocked in medium supplemented with 2% horse serum. The differentiation ability of AS clones was heterogeneous, ranging from clones with a percentage of myosin-positive cells higher than controls to clones with a negligible myosin expression. Therefore, the growth impairment determined by the loop interruption is not sufficient to switch on the differentiation program. The role played by EGF-R in the proliferation of human rhabdomyosarcoma cells suggests that this receptor could constitute a target for a therapeutic approach.

¹ This work was supported by grants from TELETHON, National Research Council, National Research Council Special Project ACRO, Associazione Italiana per la Ricerca sul Cancro, and Ministero dell'Università e della Ricerca Scientifica e Tecnologica, Italy. I. R. is the recipient of a Fellowship from the Associazione Italiana per la Ricerca sul Cancro.

² To whom requests for reprints should be addressed. Fax: 39-51-242169.

Received 6/10/96. Accepted 7/16/96.

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