Cyclin a but not cyclin D1 is essential for c‐myc‐modulated cell‐cycle progression

Qi, Yitao; Tu, Yiding; Yang, Di; Chen, Qian; Xiao, Jun; Chen, Yiqiang; Fu, Junjie; Xiao, Xilong; Zong-can, Zhou

doi:10.1002/jcp.20816

Cited by 44 publications

(33 citation statements)

References 43 publications

(49 reference statements)

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“…A recent work also demonstrated that c-Myc is a target of lapatinib in gastric cancer cell lines [25]. In addition, these data are consistent with other reports demonstrating that cyclin A is critical for c-Myc-modulated cell cycle progression [26]. Therefore, lapatinib inhibition of cyclin A may subsequently abrogate c-Myc and, in turn, induce G1 phase arrest in A549 cells.…”

Section: Discussionsupporting

confidence: 87%

Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model

et al. 2010

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BackgroundThere is strong evidence demonstrating that activation of epidermal growth factor receptors (EGFRs) leads to tumor growth, progression, invasion and metastasis. Erlotinib and gefitinib, two EGFR-targeted agents, have been shown to be relevant drugs for lung cancer treatment. Recent studies demonstrate that lapatinib, a dual tyrosine kinase inhibitor of EGFR and HER-2 receptors, is clinically effective against HER-2-overexpressing metastatic breast cancer. In this report, we investigated the activity of lapatinib against non-small cell lung cancer (NSCLC).MethodsWe selected the lung cancer cell line A549, which harbors genomic amplification of EGFR and HER-2. Proliferation, cell cycle analysis, clonogenic assays, and signaling cascade analyses (by western blot) were performed in vitro. In vivo experiments with A549 cells xenotransplanted into nude mice treated with lapatinib (with or without radiotherapy) were also carried out.ResultsLapatinib dramatically reduced cell proliferation (P < 0.0001), DNA synthesis (P < 0.006), and colony formation capacity (P < 0.0001) in A549 cells in vitro. Furthermore, lapatinib induced G1 cell cycle arrest (P < 0.0001) and apoptotic cell death (P < 0.0006) and reduced cyclin A and B1 levels, which are regulators of S and G2/M cell cycle stages, respectively. Stimulation of apoptosis in lapatinib-treated A549 cells was correlated with increased cleaved PARP, active caspase-3, and proapoptotic Bak-1 levels, and reduction in the antiapoptic IAP-2 and Bcl-xL protein levels. We also demonstrate that lapatinib altered EGFR/HER-2 signaling pathways reducing p-EGFR, p-HER-2, p-ERK1/2, p-AKT, c-Myc and PCNA levels. In vivo experiments revealed that A549 tumor-bearing mice treated with lapatinib had significantly less active tumors (as assessed by PET analysis) (P < 0.04) and smaller in size than controls. In addition, tumors from lapatinib-treated mice showed a dramatic reduction in angiogenesis (P < 0.0001).ConclusionOverall, these data suggest that lapatinib may be a clinically useful agent for the treatment of lung cancer.

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Section: Discussionsupporting

confidence: 87%

Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model

et al. 2010

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“…In agreement with previous studies (14,43), one of the major cell cycle inhibitory proteins, p27, was increased following c-MYC depletion. Similarly, decreased levels of CDK4 and cyclin D3 following c-MYC silencing probably occurred by the ability of c-MYC to transcriptionally regulate the expression of these proteins (44). …”

Section: Discussionmentioning

confidence: 99%

Targeting c-MYC in Platinum-Resistant Ovarian Cancer

Reyes-González

Armaiz-Peña

Mangala

et al. 2015

Molecular Cancer Therapeutics

100

109

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The purpose of this study was to investigate the molecular and therapeutic effects of small-interfering RNA (siRNA)-mediated c-MYC silencing in cisplatin-resistant ovarian cancer. Statistical analysis of patient’s data extracted from The Cancer Genome Atlas (TCGA) portal showed that the progression free- (PFS) and the overall (OS) survival were decreased in ovarian cancer patients with high c-MYC mRNA levels. Furthermore, analysis of a panel of ovarian cancer cell lines showed that c-MYC protein levels were higher in cisplatin-resistant cells when compared to their cisplatin-sensitive counterparts. In vitro cell viability, growth, cell cycle progression, and apoptosis, as well as in vivo therapeutic effectiveness in murine xenograft models, were also assessed following siRNA-mediated c-MYC silencing in cisplatin-resistant ovarian cancer cells. Significant inhibition of cell growth and viability, cell cycle arrest, and activation of apoptosis, were observed upon siRNA-mediated c-MYC depletion. In addition, single weekly doses of c-MYC-siRNA incorporated into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG-2000)-based nanoliposomes resulted in significant reduction in tumor growth. These findings identify c-MYC as a potential therapeutic target for ovarian cancers expressing high levels of this oncoprotein.

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“…This is not surprising as c-myc has been shown in several in vitro systems to inhibit cyclin D1 expression (13)(14)(15)(16)(17) and attenuate the cell cycle-dependent cyclin D1 oscillation (18). Moreover, c-Myc-modulated cell cycle progression does not require cyclin D1 (19) but, instead, can be elicited via induction of cyclin D2 in at least certain cell types (20)(21)(22)(23). Collectively, these data indicate a possibility that c-Myc and cyclin D1 may mediate mammary carcinogenesis via different pathways.…”

Section: Introductionmentioning

confidence: 94%

Synergistic Effect of Cyclin D1 and c-Myc Leads to More Aggressive and Invasive Mammary Tumors in Severe Combined Immunodeficient Mice

et al. 2007

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Cyclin D1 is one of the most commonly overexpressed oncogenes in breast cancer; yet, it is not clear whether cyclin D1 alone is capable of causing malignant transformation of mammary epithelial cells. Here, we show that ectopic expression of cyclin D1 in benign mouse mammary epithelial cells promotes cell proliferation, anchorage-independent growth in soft agar, and tumorigenesis in severe combined immunodeficient mice. To address the possible interaction of cyclin D1 and c-myc in malignant transformation, we used cyclin D1/c-myc dual-expressing clones, which displayed more aggressive and invasive phenotype than cyclin D1-expressing clones. These data provide evidence that overexpression of cyclin D1 or coexpression with c-myc could cause invasive malignant transformation of benign mouse mammary epithelial cells. Furthermore, microarray analysis of cyclin D1 and cyclin D1/c-myc clones showed that these two tumorproducing clones might use distinct invasive pathways. In summary, overexpression of cyclin D1 may commit mammary epithelia to a tumor-prone phenotype in which cooperation with other genes, such as synergy with c-myc, may lead to a more aggressive phenotype. [Cancer Res 2007;67(8):3698-707]

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Cyclin a but not cyclin D1 is essential for c‐myc‐modulated cell‐cycle progression

Cited by 44 publications

References 43 publications

Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model

Antitumor and antiangiogenic effect of the dual EGFR and HER-2 tyrosine kinase inhibitor lapatinib in a lung cancer model

Targeting c-MYC in Platinum-Resistant Ovarian Cancer

Synergistic Effect of Cyclin D1 and c-Myc Leads to More Aggressive and Invasive Mammary Tumors in Severe Combined Immunodeficient Mice

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