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Expression of mRNA for epidermal growth factor, transforming growth factor-alpha and their receptor in human prostate tissue and cell lines

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Abstract

Enhanced expression of the epidermal growth factor receptor (EGFR) or its ligands, epidermal growth factor (EGF) and transforming growth factor alpha (TGF-α) can increase signalling via receptor-mediated pathways which may lead to excessive proliferation and cellular transformation. Such autocrine regulation of growth has been demonstrated for prostate cancer cell lines in culture but its role in prostate cancerin vivo has not been established. To assess the potential of such a mechanism, we have examined the pathway components in prostate carcinomas (CaP) in comparison with non-malignant benign prostatic hyperplasias (BPH). In the present study, we investigate the dosage, structure and expression of EGF, TGF-α and EGFR genes in a series of 34 human prostate samples and 3 prostate cancer cell lines. All of the samples contained transcripts from each of the genes. The expression of pre-pro-TGF-α mRNA and pre-pro-EGF mRNA were significantly higher in CaP (n=13) than BPH (n=21) specimens (p<0.05). The androgen-responsive prostatic carcinoma cell line, LNCaP, expressed high levels of EGF mRNA while the androgen-independent DU145 and PC-3 cell lines expressed high levels of TGF-α mRNA and EGFR mRNA. In general, overexpression of these mRNAs was not associated with amplification or detectable gene rearrangment; only DU145 cells demonstrated any alteration in these genes, with apparent amplification of the TGF-α gene. Relative to BPH, all prostate carcinomas and cell lines studied had elevated levels of mRNA for one or both mRNA coding for the ligands for EGFR. Thus enhanced expression of the ligands and co-expression of the EGF receptor are frequent events in human prostate tumors, consistent with the cell culture data supporting autocrine growth regulation via EGFR-mediated pathways.

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Authors and Affiliations

  1. Department of Physiology, University of Manitoba, R3E 0W3, Winnipeg, Manitoba, Canada

    Karen Z. Ching & Janice G. Dodd

  2. Section of Urology, Department of Surgery, University of Manitoba, R3E 0W3, Winnipeg, Manitoba, Canada

    E. Ramsey

  3. Department of Pathology, University of Manitoba, R3E 0W3, Winnipeg, Manitoba, Canada

    N. Pettigrew & R. D'Cunha

  4. Department of Urology, Seven Oaks General Hospital, Winnipeg, Manitoba, Canada

    M. Jason

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  1. Karen Z. Ching
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  2. E. Ramsey
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  3. N. Pettigrew
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  4. R. D'Cunha
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  5. M. Jason
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  6. Janice G. Dodd
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Ching, K.Z., Ramsey, E., Pettigrew, N. et al. Expression of mRNA for epidermal growth factor, transforming growth factor-alpha and their receptor in human prostate tissue and cell lines. Mol Cell Biochem 126, 151–158 (1993). https://doi.org/10.1007/BF00925693

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  • DOI: https://doi.org/10.1007/BF00925693

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