c-Myc Regulates Cyclin D-Cdk4 and -Cdk6 Activity but Affects Cell Cycle Progression at Multiple Independent Points

Mateyak, Maria K.; Obaya, Álvaro J.; Sedivy, John M.

doi:10.1128/mcb.19.7.4672

Cited by 293 publications

(256 citation statements)

References 119 publications

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“…The growth curves presented here extend earlier work of others (Mateyak et al, 1999), which showed that ectopic expression of cyclin D1, cyclin E and cyclin A did not revert the c-myc null phenotype. Our data indicate that many of the genes that act in G1 to S phase transition are not responsible for the growth defect of the c-myc null cells.…”

Section: Abstract: C-myc; Cell Proliferation; Cell Cyclesupporting

confidence: 88%

“…These cmyc 7/7 cells are viable but proliferate approximately three times slower than their wild type counterparts, a phenotype that can be rescued by ectopic expression of c-myc (Mateyak et al, 1997). It was shown that cmyc 7/7 cells have a reduced activity of all cyclin/CDK complexes, and CDK7 and p27 were implicated as downstream e ectors of c-Myc (Mateyak et al, 1999). Interestingly, when these cells were analysed for expression of several putative c-Myc-regulated genes, only the expression of cad and gadd45 appeared to be a ected, suggesting that many of the proposed c-Mycactivated genes do not contribute to the growth defect of the c-myc null cells (Bush et al, 1998).…”

Section: Abstract: C-myc; Cell Proliferation; Cell Cyclementioning

confidence: 99%

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A genetic screen to identify genes that rescue the slow growth phenotype of c-myc null fibroblasts

et al. 2000

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Section: Abstract: C-myc; Cell Proliferation; Cell Cyclesupporting

confidence: 88%

Section: Abstract: C-myc; Cell Proliferation; Cell Cyclementioning

confidence: 99%

A genetic screen to identify genes that rescue the slow growth phenotype of c-myc null fibroblasts

et al. 2000

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“…Thus, c-Myc-mediated inhibition of p21 WAF1 transactivation described herein for K562 may occur widely among tumor cells. Other recent studies show that loss of c-Myc in rat Rat-1 cells results in a reduction of p21 WAF1 (Mateyak et al, 1999). This reinforces the idea that c-Myc does not directly interact with p21 WAF1 or Bax promoters and that the e ect on p53 transcriptional activity depends on the cell type.…”

Section: Discussionsupporting

confidence: 76%

“…Immunocomplexes were detected with peroxidase-conjugated secondary antibodies (Cappel) and chemiluminescent method (ECL, Amersham). For kinase assays, cyclin E and CDK2 immunoprecipitations were performed essentially as described (Mateyak et al, 1999), using anti-cyclin E (M-20, Santa Cruz) and anti-CDK2 (M2, Santa Cruz) antibodies. Kinase activity of the immunoprecipitates was assayed using histone H1 as substrate.…”

Section: Rna Protein and Kinase Activity Analysismentioning

confidence: 99%

c-Myc antagonizes the effect of p53 on apoptosis and p21WAF1 transactivation in K562 leukemia cells

et al. 2000

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c-myc protooncogene positively regulates cell proliferation and overexpression of c-myc is found in many solid tumors and leukemias. In the present study we used the K562 human myeloid leukemia cell line as a model to study the functional interaction between c-Myc and p53. Using two di erent methods, we generated K562 transfectant cell lines with conditional expression of either c-Myc or p53. The cells expressed the p53 Vall35 mutant, which adopts a wild-type conformation at 328C, while c-Myc induction was achieved with a zinc-inducible expression vector. We found that p53 in wild-type conformation induces growth arrest and apoptosis of K562. Expression of c-Myc signi®cantly attenuated apoptosis and impaired the transcriptional activity of p53 on p21 WAF1 , Bax and cytomegalovirus promoters. The impairment of p21 WAF1 transactivation by c-Myc was con®rmed by transfection of a c-Myc-estrogen receptor fusion protein and by induction of c-myc by zinc in transfected cells. Also, p53-mediated up-regulation of p21 WAF1 mRNA protein were signi®cantly reduced by cMyc, while Bax levels were una ected. Consistently, cMyc increased cyclin-dependent kinase 2 activity in K562 cells expressing p53 in wild-type conformation. These results suggest that c-Myc overexpression may antagonize the pro-apoptotic function of p53, thus providing a molecular mechanism for the frequently observed deregulation of c-myc in human cancer.

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“…Interestingly, in good prognosis patients (no recurrence during 10 years of follow-up), FXR expression was correlated with several proliferation factors (cyclin D and p27), whereas in the poor outcome patients (distant metastasis), it was exclusively correlated with c-myc. Of note, c-myc and cyclin D1 participate in the activation of the cyclin E-cdk2 complexes by overriding the cell cycle arrest imposed by p27 overexpression [35]. No definite conclusion can, however, be drawn since the number of patients with poor prognosis was low.…”

Section: Discussionmentioning

confidence: 99%

Association between farnesoid X receptor expression and cell proliferation in estrogen receptor-positive luminal-like breast cancer from postmenopausal patients

Journé

Durbecq

Chaboteaux

et al. 2008

Breast Cancer Res Treat

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International audienceThe farnesoid X receptor (FXR, NR1H4), a member of the nuclear receptor superfamily of ligand-dependent transcription factors, is normally produced in the liver and the gastrointestinal tract, where it acts as a bile acid sensor. It has been recently detected in breast cancer cell lines and tissue specimens. The expression of FXR was scored (0–8) by immunohistochemistry on 204 breast cancer samples and correlated with established cancer biomarkers. Moreover, the effect of the FXR activator chenodeoxycholic acid (CDCA) was determined on cell proliferation and estrogen receptor regulation/activation in breast cancer cell lines. FXR was detected in 82.4% of samples with a high median expression score of 5. FXR expression significantly correlated with estrogen receptor (ER) expression ( = 0.009) and luminal-like markers. In ER-positive tumors, FXR expression was significantly correlated with the proliferation marker Ki-67 ( < 0.001) and the nodal status ( = 0.028), but only so in postmenopausal women, suggesting that lack of estrogens may disclose the association between FXR and cell proliferation. In vitro experiments confirmed clinical data since CDCA stimulated the proliferation of ER-positive cells only in steroid-free medium, a stimulation inhibited upon siRNA-silencing of FXR expression as well as ER blockade by antiestrogens. Moreover, co-immunoprecipitation experiments revealed that CDCA activated-FXR interacted with ER. These results suggest that ER-positive breast tumors could be stimulated to proliferate via a crosstalk between FXR and ER, particularly in a state of estrogen deprivation (menopause, aromatase inhibitors)

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c-Myc Regulates Cyclin D-Cdk4 and -Cdk6 Activity but Affects Cell Cycle Progression at Multiple Independent Points

Cited by 293 publications

References 119 publications

A genetic screen to identify genes that rescue the slow growth phenotype of c-myc null fibroblasts

A genetic screen to identify genes that rescue the slow growth phenotype of c-myc null fibroblasts

c-Myc antagonizes the effect of p53 on apoptosis and p21WAF1 transactivation in K562 leukemia cells

Association between farnesoid X receptor expression and cell proliferation in estrogen receptor-positive luminal-like breast cancer from postmenopausal patients

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