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

Sherwood, Edward R.; Dongen, Jennifer L. Van; Wood, Christopher G.; Liao, Shutsung; Kozlowski, James M.; Lee, C.

doi:10.1038/bjc.1998.142

Cited by 112 publications

(69 citation statements)

References 33 publications

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“…It has been suggested that upregulation of EGFR is involved in the development of AIPC [24][25][26]. In addition, the AIPC cell line PC3 was found to express higher levels of EGFR than the LNCaP cell line [1]. These findings provide additional evidence supporting the hypothesis that EGFR expression has a role in the development of AIPC.…”

Section: Discussionsupporting

confidence: 63%

“…EGFR signalling might be one of the most critical signalling mechanisms for cancer cells, including prostate cancer cells [1,3,10]. To investigate the effects of EGFR on PC3 cells, we analysed signalling molecules Figure 2.…”

Section: Exogenous Expression Of P27 Inhibits Egfr/pi3k/ Akt Signallimentioning

confidence: 99%

“…EGFR has a critical role in tumour growth, and prostate tissue becomes more susceptible to the growth-promoting action of EGF family growth factors during androgen withdrawal [1,2]. The general inhibition of tyrosine kinase signalling pathways provides a therapeutic advantage against prostate cancer metastasis [3].…”

Section: Introductionmentioning

confidence: 99%

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Exogenous p27KIP1 expression induces anti-tumour effects and inhibits the EGFR/PI3K/Akt signalling pathway in PC3 cells

Xia¹,

Luo²,

Wang³

2009

Asian J Androl

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Abstractp27 is a cyclin-dependent kinase inhibitor that regulates the progression of cells from G 1 to S phase of the cell cycle. Loss of p27 has been associated with disease progression and with an unfavourable outcome in prostate cancer. In this study, we investigated whether exogenous p27 expression in the human androgen-independent prostate cancer PC3 cell line had any effect on cell growth, and we studied the molecular mechanisms involved. p27 expression was restored in PC3 cells by plasmid delivery. Cell proliferation and apoptosis were assessed in PC3 cells transfected with p27. We also investigated the effects of p27 on the epidermal growth factor receptor (EGFR)/ phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway in PC3 cells. By restoring p27 expression in PC3 cells, we observed that p27 reduced proliferation and induced arrest in G 0 /G 1 phase. Moreover, p27-transfected PC3 cells underwent apoptosis, as shown by flow cytometric analysis and western blotting analysis of Bcl-2, Bax, Bad, caspase-3 and poly(ADP-ribose)polymerase expression. Furthermore, the p27-induced anti-tumour action correlated with inhibition of the EGFR/PI3K/Akt signalling pathway, as confirmed by western blotting analysis and densitometry of EGFR, PI3K (p85), Akt and p-Akt S473 expression. Our results suggest that exogenous expression of p27 inhibits the proliferation of PC3 cells through induction of G 1 arrest and apoptosis, and this process correlates with inhibition of the EGFR/PI3K/Akt signalling pathway.

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Section: Discussionsupporting

confidence: 63%

Section: Exogenous Expression Of P27 Inhibits Egfr/pi3k/ Akt Signallimentioning

confidence: 99%

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Exogenous p27KIP1 expression induces anti-tumour effects and inhibits the EGFR/PI3K/Akt signalling pathway in PC3 cells

Xia¹,

Luo²,

Wang³

2009

Asian J Androl

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“…Several groups have demonstrated the role of increased EGFR signaling in prostate carcinogenesis and progression (Sherwood et al, 1998;Ratan et al, 2003;Torring et al, 2003). We have recently reported the discovery of four somatic missense mutations in the tyrosine kinase domain of EGFR in prostate cancer patients (Douglas et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Epidermal growth factor receptor activation in prostate cancer by three novel missense mutations

et al. 2008

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While epidermal growth factor receptor (EGFR) dysregulation is known to play a critical role in prostate carcinogenesis, there has been no direct evidence indicating EGFR mutations induce tumorigenesis in prostate cancer. We previously identified four novel EGFR somatic mutations in the EGFR tyrosine kinase domain of prostate cancer patients: G735S, G796S, E804G and R841K. In this study, we investigated the oncogenic potential of these somatic mutations by establishing stable clonal NIH3T3 cells expressing these four mutations and WT EGFR to determine their ability to increase cell proliferation and invasion. In the absence of the EGF ligand, cell proliferation was readily increased in G735S, G796S and E804G mutants compared to WT EGFR. The addition of EGF ligand greatly increased cell growth and transforming ability of these same EGFR mutants. Matrigel invasion assays showed enhanced invasion with G735S, G796S and E804G mutants. Western blot analysis showed that these EGFR mutations enhanced cell growth and invasion via constitutive and hyperactive tyrosine phosphorylation and led to the activation of mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3) and Akt pathways. Our findings demonstrate the oncogenic activation of three novel EGFR somatic missense mutations in prostate cancer. Molecules that regulate the mechanisms of their oncogenic activation represent novel targets for limiting tumor cell progression, and further elucidation of these mutations will have utility in prostate cancer treatment.

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“…109,120,121 In addition, assessment of the relative expression and autocrine activation of the EGFR in normal and transformed prostatic epithelial cells has shown that human androgen-independent prostate cancer cell lines (PC-3 and DU145) exhibited higher levels of EGFR expression and autocrine phosphorylation than normal human prostatic epithelial cells, or human androgen-responsive prostate cancer cells (LNCaP). 122 It seems that autocrine activation of EGFR is a common feature of prostatic carcinoma cells in contrast to normal epithelial cells. The intracellular domain of the EGFR has been shown to have partial homology with ErbB2.…”

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

Cited by 112 publications

References 33 publications

Exogenous p27KIP1 expression induces anti-tumour effects and inhibits the EGFR/PI3K/Akt signalling pathway in PC3 cells

Exogenous p27KIP1 expression induces anti-tumour effects and inhibits the EGFR/PI3K/Akt signalling pathway in PC3 cells

Epidermal growth factor receptor activation in prostate cancer by three novel missense mutations

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

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