New Advances on Prostate Carcinogenesis and Therapies: Involvement of EGF-EGFR Transduction System

Mimeault, Murielle; Pommery, Nicole; Hénichart, Jean‐Pierre

doi:10.1080/0897719031000094921

Cited by 50 publications

(71 citation statements)

References 103 publications

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“…In this manner, neuroendocrine cells may activate an alternative antiapoptotic mechanism that can support tumor growth in the presence of PI3K and EGFR inhibitors. Reports on synergism between inhibitors of PKA and EGFR kinases in prostate cells and colon tumor xenografts provide circumstantial evidence that support the significance of interaction between EGFR and PKA signaling (68,69). It remains to be seen if BAD phosphorylation forms the basis for this synergism, as it was recently demonstrated for inducible expression of PTEN and EGFR inhibitor in breast cancer xenografts (59).…”

Section: Discussionmentioning

confidence: 99%

Diverse Antiapoptotic Signaling Pathways Activated by Vasoactive Intestinal Polypeptide, Epidermal Growth Factor, and Phosphatidylinositol 3-Kinase in Prostate Cancer Cells Converge on BAD

Sastry

Smith

Karpova

et al. 2006

Journal of Biological Chemistry

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It has been demonstrated that vasoactive intestinal polypeptide, epidermal growth factor, and chronic activation of phosphatidylinositol 3-kinase can protect prostate cancer cells from apoptosis; however, the signaling pathways that they use and molecules that they target are unknown. We report that vasoactive intestinal polypeptide, epidermal growth factor, and phosphatidylinositol 3-kinase activate independent signaling pathways that phosphorylate the proapoptotic protein BAD. Vasoactive intestinal polypeptide operated via protein kinase A, epidermal growth factor required Ras activity, and effects of phosphatidylinositol 3-kinase were predominantly mediated by Akt. BAD phosphorylation was critical for the antiapoptotic effects of each signaling pathway. None of these survival signals was able to rescue cells that express BAD with mutations in phosphorylation sites, whereas knockdown of BAD expression with small hairpin RNA rendered cells insensitive to apoptosis. Taken together, these results identify BAD as a convergence point of several antiapoptotic signaling pathways in prostate cells.

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Section: Discussionmentioning

confidence: 99%

Diverse Antiapoptotic Signaling Pathways Activated by Vasoactive Intestinal Polypeptide, Epidermal Growth Factor, and Phosphatidylinositol 3-Kinase in Prostate Cancer Cells Converge on BAD

Sastry

Smith

Karpova

et al. 2006

Journal of Biological Chemistry

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“…Activated EGFR may induce distinct mitotic cascades, including the MAPK, PI3K/Akt, Shc, NF-κB and phospholipase Cg signalling pathways, which stimulate the proliferation, survival, motility and invasiveness of prostate cancer cells [29][30][31][32]. Elevated Akt activity may have a profound role in the progression of human prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

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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“…24,26 Additionally, the epidermal growth factor receptor (EGFR) and its ligands, epidermal growth factor (EGF) and transforming growth factor-a (TGF-a), which assume an important role for normal prostate development, [27][28][29][30] are also overexpressed during the progression of benign, localized and metastatic forms of PC. [31][32][33][34] The upregulated activation of EGFR signaling appears notably to contribute to the sustained cell proliferation, survival and invasion of PC epithelial cells. 27,29,[31][32][33]35,36 It has also been reported that the blockade of either HH or EGF-EGFR signaling, by using a selective SMO or EGFR inhibitor, such as cyclopamine and gefitinib (also known as Iressa or ZD1839), respectively, leads to the growth inhibition and apoptotic death of many cancer cell types, including prostate tumor epithelial cells in vivo and in vitro.…”

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confidence: 99%

Cytotoxic effects induced by a combination of cyclopamine and gefitinib, the selective hedgehog and epidermal growth factor receptor signaling inhibitors, in prostate cancer cells

Mimeault

Moore

Moniaux

et al. 2005

Intl Journal of Cancer

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118

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Although the blockade of the hedgehog cascade by using cyclopamine has been reported to inhibit the growth of some cancer cell types, few studies on the mechanism by which this drug alone or in combination with other cytotoxic agents induces its cytotoxic effect have been reported. In our study, we evaluate, for the first time, the antiproliferative and cytotoxic effects induced by a combination of selective SMO inhibitor, cyclopamine and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib on metastatic prostate cancer (PC) cells. The results revealed that cyclopamine, alone or at a lower concentration in combination with gefitinib, inhibited the growth of sonic hedgehog-(SHH), epidermal growth factor-(EGF) and serum-stimulated androgensensitive LNCaP-C33 and LNCaP-LN3 and androgen-independent LNCaP-C81, DU145 and PC3 cells. The antiproliferative effect of cyclopamine and gefitinib, alone or in combination, was mediated via a blockade of the PC3 cells in the G1 phase of the cell cycle. Importantly, the combined cyclopamine and gefitinib also caused a higher rate of apoptotic death of PC cells compared to single agents. The cytotoxic effect induced by these drugs in PC3 cells appears to be mediated at least, in part, via the mitochondrial pathway through the depolarization of the mitochondrial membrane and the release of cytochrome c and reactive oxygen species into the cytosol. This was also accompanied by the activation of caspase cascades, PARP cleavage and DNA fragmentation. Additionally, the combined cyclopamine and gefitinib were more effective at suppressing the invasiveness of PC3 cells through matrigel in vitro as the drugs alone. These findings indicate that the simultaneous blockade of SHH-GLI-1 and EGF-EGFR signaling, which results in the growth arrest and massive rate of apoptotic cell death, represents a promising strategy for a more effective treatment of metastatic PC forms. ' 2005 Wiley-Liss, Inc.

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New Advances on Prostate Carcinogenesis and Therapies: Involvement of EGF-EGFR Transduction System

Cited by 50 publications

References 103 publications

Diverse Antiapoptotic Signaling Pathways Activated by Vasoactive Intestinal Polypeptide, Epidermal Growth Factor, and Phosphatidylinositol 3-Kinase in Prostate Cancer Cells Converge on BAD

Diverse Antiapoptotic Signaling Pathways Activated by Vasoactive Intestinal Polypeptide, Epidermal Growth Factor, and Phosphatidylinositol 3-Kinase in Prostate Cancer Cells Converge on BAD

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

Cytotoxic effects induced by a combination of cyclopamine and gefitinib, the selective hedgehog and epidermal growth factor receptor signaling inhibitors, in prostate cancer cells

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