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

Ching, Karen; Ramsey, Ernest W.; Pettigrew, Norman M.; Dcunha, Reyon; Jason, M.; Dodd, Janice G.

doi:10.1007/bf00925693

Cited by 88 publications

(69 citation statements)

References 32 publications

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“…Moreover, recent data indicate that chimeric monoclonal EGFR antibodies can significantly inhibit the growth of DU145 and PC3 cell xenografts in nude mice (Prewett et al, 1997). Analysis of the responses to EGF and TGF-α in the androgen-independent DU145 and PC3 cell lines which overexpress EGFRs suggests that part of the progression to hormone-independence involves a 'switch' in secretion from EGF to TGF-α (Ching et al, 1993), and development of an autocrine loop. Evidence supporting the existence of an autocrine loop involving TGF-α and the EGFR has been obtained in prostate carcinoma specimens (Glynne-Jones et al, 1996), as well as in prostate cancer cell lines (Ching et al, 1993;Liu et al, 1993).…”

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confidence: 99%

“…The epidermal growth factor receptor (EGFR) and two of its multiple high affinity ligands, EGF and TGF-α, play an important role in the development of several different human cancers (Todaro et al, 1979;Lippman, 1993), including prostate cancer (Ching et al, 1993). Several studies have shown that prostate cancer cells express EGF, TGF-α and EGFR mRNA and protein (Morris and Dodd, 1990;Ching et al, 1993;Glynne-Jones et al, 1996).…”

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confidence: 99%

“…The latter cell line is highly invasive and metastatic, and has greatly increased EGFRs (Zhau et al, 1996). Most of these cell lines are growth-stimulated by EGF and TGF-α in culture (Davies and Eaton, 1989;Ching et al, 1993), and growth-inhibited by EGFR antibodies (Ennis et al, 1989;Mendelsohn, 1992). Moreover, recent data indicate that chimeric monoclonal EGFR antibodies can significantly inhibit the growth of DU145 and PC3 cell xenografts in nude mice (Prewett et al, 1997).…”

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confidence: 99%

“…Several studies have shown that prostate cancer cells express EGF, TGF-α and EGFR mRNA and protein (Morris and Dodd, 1990;Ching et al, 1993;Glynne-Jones et al, 1996). Further, recent immunohistochemical and in situ hybridization analysis showed that the levels of EGFR and TGF-α mRNA and protein are increased in carcinoma cells compared to benign epithelium (Ching et al, 1993;Glynne-Jones et al, 1996). Overexpression of the EGFR is also associated with a worse clinical prognosis (Gullick, 1991;Modjtahedi and Dean, 1994).…”

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confidence: 99%

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Complex post-transcriptional regulation of EGF-receptor expression by EGF and TGF-α in human prostate cancer cells

et al. 1999

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SummaryThe epidermal growth factor receptor (EGFR) plays an important role in the development and progression of prostate cancer and its overexpression is associated with decreased survival. With progression, prostate cancer cells switch from epidermal growth factor (EGF) to transforming growth factor α (TGF-α) synthesis, which contributes to autocrine growth and unrestrained proliferation. To define the molecular mechanisms involved in the regulation of EGFR expression by EGF and TGF-α we studied three human prostate cancer cell lines, androgen-responsive (LNCaP) and -unresponsive (DU145 and PC3). Here we show that TGF-α stabilized EGFR mRNA two-to threefold in all three cell lines, whilst EGF stabilized EGFR mRNA ~ twofold in LNCaP and DU145 cells, but not in PC3 cells. Both ligands increased EGFR transcription in LNCaP and DU145 cells, with less effect in PC3 cells. In all three cell lines EGF reduced total EGFR protein levels more than TGF-α, but this was associated with a greater increase in de novo protein synthesis with EGF compared to TGF-α. Only EGF, however, shortened EGFR protein stability (half-life decreased from 5 h to 120 min), resulting in rapid disappearance of newly synthesized EGFR protein. Both ligands increased total LNCaP and DU145 cell numbers. These studies demonstrate that the EGF-and TGF-α-induced upregulation of EGFR mRNA and protein in human prostate cancer cell lines is complex and occurs at multiple, transcriptional and post-transcriptional levels. Taken together, these data provide novel insight into the molecular mechanisms by which TGF-α would preferentially maintain an autocrine loop in human prostate cancer cells. Furthermore, this work suggests that in human prostate cancer cells ligand-specific differential intracellular trafficking of the EGFR plays a major role in regulating its expression.

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confidence: 99%

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confidence: 99%

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Complex post-transcriptional regulation of EGF-receptor expression by EGF and TGF-α in human prostate cancer cells

et al. 1999

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“…In addition, it has been suggested that the progression to the androgen-independent state may involve a switch in the predominant ligand from EGF to TGF-a. 124 In vitro studies using the DU145 cell line have shown that EGFR-mediated signals enhance cell transmigration of an extracellular matrix. This increased invasiveness has been shown to be independent of proteolytic degradation of the matrix 125 and not due to altered growth.…”

Section: Egf and Tgf-amentioning

confidence: 99%

Molecular and cellular biology of prostate cancer—the role of apoptosis as a target for therapy

Costa-Pereira

Cotter

1999

Prostate Cancer Prostatic Dis

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Despite the high incidence and mortality rate of prostate cancer, the molecular mechanisms underlying the progression of the disease remain to be fully elucidated. This paper reviews the current state of knowledge on prostatic carcinogenesis, focusing not only on the molecular genetics of prostate cancer, but also on the role of oncogenes, tumour suppressor genes, and growth factors. The remarkable ability of prostate cancer cells to survive androgen withdrawal and apoptosis are discussed, with particular emphasis on how apoptosis may be manipulated from a therapeutic viewpoint.

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The molecular pathology of urological malignancies

1997

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Urological malignancies kill over 16 000 people annually in England and Wales. There have been exciting recent developments in our understanding of the molecular pathogenesis of these diseases, although many questions remain unanswered. Three separate genes (WT1, WT2, and WT3) have been implicated in Wilms' tumour development. Patients with von Hippel–Lindau (VHL) syndrome develop renal cell carcinoma and it has been shown that VHL protein inhibits elongin, a cellular transcription factor which controls RNA elongation. Use of molecular markers to identify superficial bladder tumours likely to progress to muscle invasive disease has met with some success. Increased epidermal growth factor receptor (EGFR) and p53 expression, and decreased E‐cadherin expression all correlate with tumour progression. Tumours in patients with carcinoma in situ have distinct molecular features. Androgen ablation delays disease progression in men with prostate cancer, but relapse is inevitable. Research has been directed towards elucidating the mechanisms by which prostate cancer ‘escapes’ hormonal control. Mutations in the androgen receptor have been identified. It is apparent that locally produced growth factors mediate androgen‐dependent processes and these too have been implicated in prostate carcinogenesis. © 1997 John Wiley & Sons, Ltd.

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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

Cited by 88 publications

References 32 publications

Complex post-transcriptional regulation of EGF-receptor expression by EGF and TGF-α in human prostate cancer cells

Complex post-transcriptional regulation of EGF-receptor expression by EGF and TGF-α in human prostate cancer cells

Molecular and cellular biology of prostate cancer—the role of apoptosis as a target for therapy

The molecular pathology of urological malignancies

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