Binding of epidermal growth factor by human normal, hypertrophic, and carcinomatous prostate

Davies, Peter J.; Eaton, Colby L.

doi:10.1002/pros.2990140206

Cited by 88 publications

(44 citation statements)

References 34 publications

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“…Higher levels of EGFR expression in DU145 and PC3 compared with LNCaP have been reported at the transcriptional level (Morris and Dodd, 1990;Ching et al, 1993) and by ligand binding (Davies and Eaton, 1989). Our results extended those findings by showing increased EGFR expression at the translational level in PC3 and DU145 cells.…”

Section: Discussionsupporting

confidence: 87%

“…In addtiion, our studies demonstrated that androgen-independent but not androgen-sensitive, prostatic tumour cell lines express higher levels of EGFR than normal prostatic epithelial cells. None of the in vivo studies have adequately addressed the issue of relative EGFR expression in androgen-sensitive and androgen-independent prostate cancer, although Davies and Eaton (1989) have reported an inverse relationship between EGF binding and androgen receptor expression in homogenized specimens of prostatic carcinoma. Results of the present study showed that elevated expression and activation of EGFR were associated with the androgenindependent phenotype.…”

Section: Discussionmentioning

confidence: 99%

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Epidermal growth factor receptor activation in androgen-independent but not androgen-stimulated growth of human prostatic carcinoma cells

Sherwood

Dongen²,

Wood³

et al. 1998

Br J Cancer

111

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Summary These studies were undertaken to assess the relative expression and autocrine activation of the epidermal growth factor receptor (EGFR) in normal and transformed prostatic epithelial cells and to determine whether EGFR activation plays a functional role in androgenstimulated growth of prostate cancer cells in vitro. EGFR expression was determined by Western blot analysis and ELISA immunoassays. Immunoprecipitation of radiophosphorylated EGFR and evaluation of tyrosine phosphorylation was used to assess EGFR activation. The human androgen-independent prostate cancer cell lines PC3 and DU145 exhibited higher levels of EGFR expression and autocrine phosphorylation than normal human prostatic epithelial cells or the human androgen-responsive prostate cancer cell line LNCaP. PC3 and DU145 cells also showed higher levels of autonomous growth under serum-free defined conditions. Normal prostatic epithelial cells expressed EGFR but did not exhibit detectable levels of EGFR phosphorylation when cultured in the absence of exogenous EGF. Addition of EGF stimulated EGFR phosphorylation and induced proliferation of normal cells. LNCaP cells exhibited autocrine phosphorylation of EGFR but did not undergo significant proliferation when cultured in the absence of exogenous growth factors. A biphasic growth curve was observed when LNCaP cells were cultured with dihydrotestosterone (DHT). Maximum proliferation occurred at 1 nM DHT with regression of the growth response at DHT concentrations greater than 1 nm. However, neither EGFR expression nor phosphorylation was altered in LNCaP cells after androgen stimulation. In addition, DHT-stimulated growth of LNCaP cells was not inhibited by anti-EGFR. These studies show that autocrine activation of EGFR is a common feature of prostatic carcinoma cells in contrast to normal epithelial cells. However, EGFR activation does not appear to play a functional role in androgen-stimulated growth of LNCaP cells in vitro.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Epidermal growth factor receptor activation in androgen-independent but not androgen-stimulated growth of human prostatic carcinoma cells

Sherwood

Dongen²,

Wood³

et al. 1998

Br J Cancer

111

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“…The presence of the EGF/TGFα receptor, previously reported in the literature (Davies & Eaton 1989), was first confirmed in the clone of cells used in our laboratory. The identity of the 170 kDa band, expected to be the EGF/ TGFα receptor, was then validated by autoradiography of the immunoprecipitated labeled phosphoproteins using a specific monoclonal antibody raised against the EGF/ TGFα receptor.…”

Section: Effects Of Somatostatin On the Phosphorylation Of The Egf/tgsupporting

confidence: 73%

Somatostatin and the phosphorylation of the epidermal growth factor/transforming growth factor alpha (TGFalpha) receptor in LNCaP cells: interactions with a locally produced TGFalpha

Brevini¹

1998

Endocrine Related Cancer

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“…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).…”

mentioning

confidence: 99%

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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Binding of epidermal growth factor by human normal, hypertrophic, and carcinomatous prostate

Cited by 88 publications

References 34 publications

Epidermal growth factor receptor activation in androgen-independent but not androgen-stimulated growth of human prostatic carcinoma cells

Epidermal growth factor receptor activation in androgen-independent but not androgen-stimulated growth of human prostatic carcinoma cells

Somatostatin and the phosphorylation of the epidermal growth factor/transforming growth factor alpha (TGFalpha) receptor in LNCaP cells: interactions with a locally produced TGFalpha

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

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