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Transforming Growth Factor-α Antisense Vectors can Inhibit Glioma Cell Growth

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Abstract

The effects of transforming growth factor-α (TGF-α) on cell growth were studied in human glioma U251 cells transfected with antisense TGF-α vectors (pcDNAI.neo). Several antisense clones showed a marked decrease in growth rate in serum-free medium but not in medium containing 10% FBS, compared with those of parental cells and clones from sense or vector transfectants. Antisense clones also produced fewer and smaller colonies in anchorage-independent growth assays. Moreover, there was a reduction in TGF-α expression in these antisense clones at both the protein and mRNA levels, as determined by enzyme linked immuno-sorbent assay and reverse transcriptase polymerase chain reaction analysis. A U251 clone transfected by TGF-α antisense in a different vector (pMT/Ep) also showed a marked suppression in cell growth and TGF-α mRNA level. Finally, transfected clones with either vector system, showed decreased tumorigenicity in nude mice. In summary, a strong correlation between the inhibition of glioma cell growth and TGF-α expression was obtained from two different plasmid vectors, indicating that the expression of TGF-α could be specifically and effectively down-regulated by TGF-α antisense vector, which in turn led to growth inhibition. These studies suggests that TGF-α plays an essential role in controlling human glioma cell proliferation and may serve as a potential target for treatment of malignant glioma.

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Authors and Affiliations

  1. Department of Neuro-oncology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, USA

    Ping Tang, Samar A. Jasser, Jeffrey C. Sung, Yuexi Shi, Peter A. Steck & W.K. Alfred Yung

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  1. Ping Tang
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  2. Samar A. Jasser
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  3. Jeffrey C. Sung
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  4. Yuexi Shi
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  6. W.K. Alfred Yung
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Tang, P., Jasser, S.A., Sung, J.C. et al. Transforming Growth Factor-α Antisense Vectors can Inhibit Glioma Cell Growth. J Neurooncol 43, 127–135 (1999). https://doi.org/10.1023/A:1006272019933

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