Epidermal growth factor induces cyclin D1 in a human prostate cancer cell line

Perry, Jaime E.; Großmann, Matthias; Tindall, Donald J.

doi:10.1002/(sici)1097-0045(19980501)35:2<117::aid-pros5>3.0.co;2-g

Cited by 95 publications

(34 citation statements)

References 23 publications

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“…Signaling pathways mediated by ErbB-1 and ErbB-2 receptors involve the activation of Ras, MAPK, and the PI3K-activated Akt pathway, which activates several nuclear proteins, including cyclin D, a protein required for cell progression from G1 to S phase [13], [38]. We confirmed that cyclin D was translocated from cytosol to nucleus by BTC treatment (data not shown).…”

Section: Discussionsupporting

confidence: 62%

Betacellulin-Induced Beta Cell Proliferation and Regeneration Is Mediated by Activation of ErbB-1 and ErbB-2 Receptors

Shin

Lee

et al. 2011

PLoS ONE

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BackgroundBetacellulin (BTC), a member of the epidermal growth factor family, is known to play an important role in regulating growth and differentiation of pancreatic beta cells. Growth-promoting actions of BTC are mediated by epidermal growth factor receptors (ErbBs), namely ErbB-1, ErbB-2, ErbB-3 and ErbB-4; however, the exact mechanism for beta cell proliferation has not been elucidated. Therefore, we investigated which ErbBs are involved and some molecular mechanisms by which BTC regulates beta cell proliferation.Methodology/Principal FindingsThe expression of ErbB-1, ErbB-2, ErbB-3, and ErbB-4 mRNA was detected by RT-PCR in both a beta cell line (MIN-6 cells) and C57BL/6 mouse islets. Immunoprecipitation and western blotting analysis showed that BTC treatment of MIN-6 cells induced phosphorylation of only ErbB-1 and ErbB-2 among the four EGF receptors. BTC treatment resulted in DNA synthetic activity, cell cycle progression, and bromodeoxyuridine (BrdU)-positive staining. The proliferative effect was blocked by treatment with AG1478 or AG825, specific tyrosine kinase inhibitors of ErbB-1 and ErbB-2, respectively. BTC treatment increased mRNA and protein levels of insulin receptor substrate-2 (IRS-2), and this was blocked by the ErbB-1 and ErbB-2 inhibitors. Inhibition of IRS-2 by siRNA blocked cell cycle progression induced by BTC treatment. Streptozotocin-induced diabetic mice injected with a recombinant adenovirus expressing BTC and treated with AG1478 or AG825 showed reduced islet size, reduced numbers of BrdU-positive cells in the islets, and did not attain BTC-mediated remission of diabetes.Conclusions/SignificanceThese results suggest that BTC exerts proliferative activity on beta cells through the activation of ErbB-1 and ErbB-2 receptors, which may increase IRS-2 expression, contributing to the regeneration of beta cells.

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Section: Discussionsupporting

confidence: 62%

Betacellulin-Induced Beta Cell Proliferation and Regeneration Is Mediated by Activation of ErbB-1 and ErbB-2 Receptors

Shin

Lee

et al. 2011

PLoS ONE

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“…Forced expression of cyclin D1 enhanced cellular proliferation in two studies (42,43) and inhibited proliferation in another study (44). Cyclin D1 physically associates with the AR in IP-Western blot analysis and forced overexpression of cyclin D1 is capable of inhibiting AR reporter gene activity (45).…”

Section: Discussionmentioning

confidence: 95%

Cyclin D1 Promotes Androgen-Dependent DNA Damage Repair in Prostate Cancer Cells

Casimiro

Sante

et al. 2016

Cancer Research

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Therapy resistance and poor outcome in prostate cancer is associated with increased expression of Cyclin D1. Androgens promote DNA double strand break repair to reduce DNA damage, and cyclin D1 was also shown to enhance DNA damage repair (DDR). In this study, we investigated the significance of cyclin D1 in androgen-induced DDR using established prostate cancer cells and prostate tissues from cyclinD1 knockout mice. We demonstrate that endogenous cyclin D1 further diminished the dihydrotestosterone (DHT)-dependent reduction of γH2AX foci in vitro. We also show that cyclin D1 was required for the androgen-dependent DNA damage response both in vitro and in vivo. Furthermore, cyclin D1 was required for androgen-enhanced DDR and radioresistance of prostate cancer cells. Moreover, microarray analysis of primary prostate epithelial cells from cyclin D1-deficient and wild-type mice demonstrated that most of the DHT-dependent gene expression changes are also cyclin D1-dependent. Collectively, our findings suggest that the hormone-mediated recruitment of cyclin D1 to sites of DDR may facilitate the resistance of prostate cancer cells to DNA damage therapies, and highlight the need to explore other therapeutic approaches in prostate cancer to prevent or overcome drug resistance.

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“…A pulse of EGF stimulation during early G1 and another at late G1 are sufficient to drive cells past the restriction point (R point), the instant at which the cell commits to the completion of the cell cycle [437,438,439]. In cancers, activating mutations to the EGFR are correlated with higher expression levels of CYCLIN D [440,441,442,443,444,445]. These types of cancers also have lower patient prognostic values.…”

Section: Signal Transductionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways

Wee

Wang

2017

Cancers

1,292

699

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The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation. These EGFR aberrations over-activate downstream pro-oncogenic signaling pathways, including the RAS-RAF-MEK-ERK MAPK and AKT-PI3K-mTOR pathways. These pathways then activate many biological outputs that are beneficial to cancer cell proliferation, including their chronic initiation and progression through the cell cycle. Here, we review the molecular mechanisms that regulate EGFR signal transduction, including the EGFR structure and its mutations, ligand binding and EGFR dimerization, as well as the signaling pathways that lead to G1 cell cycle progression. We focus on the induction of CYCLIN D expression, CDK4/6 activation, and the repression of cyclin-dependent kinase inhibitor proteins (CDKi) by EGFR signaling pathways. We also discuss the successes and challenges of EGFR-targeted therapies, and the potential for their use in combination with CDK4/6 inhibitors.

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Epidermal growth factor induces cyclin D1 in a human prostate cancer cell line

Cited by 95 publications

References 23 publications

Betacellulin-Induced Beta Cell Proliferation and Regeneration Is Mediated by Activation of ErbB-1 and ErbB-2 Receptors

Betacellulin-Induced Beta Cell Proliferation and Regeneration Is Mediated by Activation of ErbB-1 and ErbB-2 Receptors

Cyclin D1 Promotes Androgen-Dependent DNA Damage Repair in Prostate Cancer Cells

Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways

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