Myc represses the p21
            <sup>(WAF1/CIP1)</sup>
            promoter and interacts with Sp1/Sp3

Gartel, Andrei L.; Ye, Xin; Goufman, Eugene; Shianov, Pavel; Hay, Nissim; Najmabadi, Feridoon; Tyner, Angela L.

doi:10.1073/pnas.081074898

Cited by 384 publications

(312 citation statements)

References 37 publications

(45 reference statements)

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“…In addition, not only has the transcription factor c-Myc been shown to be regulated by c-Raf-1 (37), but c-Myc itself suppresses the transcription of p21 Cip1 (38). In RASFs, c-Myc has been demonstrated to be upregulated (39), especially at sites of destruction in RA joints (40).…”

Section: Discussionmentioning

confidence: 99%

Cooperation of Ras‐ and c‐Myc–dependent pathways in regulating the growth and invasiveness of synovial fibroblasts in rheumatoid arthritis

Pap

Nawrath

Heinrich

et al. 2004

Arthritis & Rheumatism

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Conclusion. The data demonstrate that Ras-and c-Myc-dependent signaling events cooperate to regulate the growth and invasiveness of RASFs. Targeting of both c-Raf-1 and c-Myc may constitute an interesting therapeutic approach in RA.Growing evidence suggests that activated synovial fibroblasts (SFs) play a pivotal role in the pathogenesis of rheumatoid arthritis (RA), a systemic disabling disease that primarily affects the joints and results in their progressive destruction (1). Such activated fibroblasts are found predominantly in the synovial lining and appear largely responsible for the progressive destruction of articular cartilage. Apart from an altered morphology (2), changes in the expression of protooncogenes (3) and tumor suppressor genes (4,5) have been demonstrated in RASFs. Among the signaling molecules Supported by grants from the Swiss National Science Foundation (SNSF 32-64142.00) and the Deutsche Forschungsgemeinschaft (DFG Pa 698/1-1, Pa 698/2-1, and Mu 1383/3-3).

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Section: Discussionmentioning

confidence: 99%

Cooperation of Ras‐ and c‐Myc–dependent pathways in regulating the growth and invasiveness of synovial fibroblasts in rheumatoid arthritis

Pap

Nawrath

Heinrich

et al. 2004

Arthritis & Rheumatism

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“…Furthermore, we have also found a higher enrichment of active chromatin marks at the p16 INK4A and p21 CIP1/WAF1 promoters and a higher enrichment of inactive chromatin marks at the hTERT promoter, which facilitate alterations in their expressions (21-22, 28, 31). promoter to facilitate its activation (40). The downregulation of c-MYC, due to the CuB treatment, thus indirectly leads to the upregulation of the p21 CIP1/WAF1 .…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin B Alters the Expression of Tumor-Related Genes by Epigenetic Modifications in NSCLC and Inhibits NNK-Induced Lung Tumorigenesis

Shukla

Khan

Kumar

et al. 2015

Cancer Prevention Research

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Non-small cell lung cancer (NSCLC) represents almost 85% of total diagnosed lung cancer. Studies have shown that combination of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors is effective against various cancers, including lung cancer. However, optimizing the synergistic dose regime is very difficult and involves adverse side effects. Therefore, in this study, we have shown that cucurbitacin B (CuB), a single bioactive triterpenoid compound, inhibits both DNMTs and HDACs starting at a very low dose of 60 nmol/L in NSCLC H1299 cells. The CuB-mediated inhibition of DNMTs and HDACs in H1299 cells leads to the reactivation of key tumor suppressor genes (TSG) such as CDKN1A and CDKN2A, as well as downregulation of oncogenes c-MYC and K-RAS and key tumor promoter gene (TPG), human telomerase reverse transcriptase (hTERT). The upregulation of TSGs and downregulation of TPG were consistently correlated with the alterations in their promoter methylation and histone modifications. This altered expression of TPG and TSGs is, at least in part, responsible for the inhibition of cellular proliferation and induction of cellular apoptosis in NSCLC. Furthermore, CuB treatment significantly inhibited the tumor incidence and multiplicity in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in A/J mice, which was associated with the induction of apoptosis and inhibition of hyperproliferation in the lung tissues. Together, our study provides new insight into the CuB-mediated epigenetic alterations and its chemotherapeutic effects on lung cancer. Cancer Prev Res; 8(6); 552-62. Ó2015 AACR.

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“…c-Myc overexpression in LoVo cells resulted in significantly increased p53 levels, which could lead to increased p21 Waf1/Cip1 levels. However, c-Myc has been shown to directly downregulate p21 Waf1/Cip1 levels (Mitchell and El-Deiry, 1999;Gartel et al, 2001). Therefore, we decided to assess the overall effects of c-Myc overexpression on the transcriptional activity of the p21 Waf1/Cip1 promoter.…”

Section: Overexpression Of C-myc Sensitises Colon Carcinoma Cells To mentioning

confidence: 99%

c-Myc overexpression sensitises colon cancer cells to camptothecin-induced apoptosis

et al. 2003

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The proto-oncogene c-Myc is overexpressed in 70% of colorectal tumours and can modulate proliferation and apoptosis after cytotoxic insult. Using an isogenic cell system, we demonstrate that c-Myc overexpression in colon carcinoma LoVo cells resulted in sensitisation to camptothecin-induced apoptosis, thus identifying c-Myc as a potential marker predicting response of colorectal tumour cells to camptothecin. Both camptothecin exposure and c-Myc overexpression in LoVo cells resulted in elevation of p53 protein levels, suggesting a role of p53 in the c-Myc-imposed sensitisation to the apoptotic effects of camptothecin. This was confirmed by the ability of PFT-a, a specific inhibitor of p53, to attenuate camptothecin-induced apoptosis. p53 can induce the expression of p21 Waf1/Cip1 , an antiproliferative protein that can facilitate DNA repair and drug resistance. Importantly, although camptothecin treatment markedly increased p21 Waf1/Cip1 levels in parental LoVo cells, this effect was abrogated in c-Mycoverexpressing derivatives. Targeted inactivation of p21 Waf1/Cip1 in HCT116 colon cancer cells resulted in significantly increased levels of apoptosis following treatment with camptothecin, demonstrating the importance of p21 Waf1/Cip1 in the response to this agent. Finally, cDNA microarray analysis was used to identify genes that are modulated in expression by c-Myc upregulation that could serve as additional markers predicting response to camptothecin. Thirty-four sequences were altered in expression over four-fold in two isogenic c-Myc-overexpressing clones compared to parental LoVo cells. Moreover, the expression of 10 of these genes was confirmed to be significantly correlated with response to camptothecin in a panel of 30 colorectal cancer cell lines.

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Myc represses the p21 ^(WAF1/CIP1) promoter and interacts with Sp1/Sp3

Cited by 384 publications

References 37 publications

Cooperation of Ras‐ and c‐Myc–dependent pathways in regulating the growth and invasiveness of synovial fibroblasts in rheumatoid arthritis

Cooperation of Ras‐ and c‐Myc–dependent pathways in regulating the growth and invasiveness of synovial fibroblasts in rheumatoid arthritis

Cucurbitacin B Alters the Expression of Tumor-Related Genes by Epigenetic Modifications in NSCLC and Inhibits NNK-Induced Lung Tumorigenesis

c-Myc overexpression sensitises colon cancer cells to camptothecin-induced apoptosis

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Myc represses the p21 (WAF1/CIP1) promoter and interacts with Sp1/Sp3

Cited by 384 publications

References 37 publications

Cooperation of Ras‐ and c‐Myc–dependent pathways in regulating the growth and invasiveness of synovial fibroblasts in rheumatoid arthritis

Cooperation of Ras‐ and c‐Myc–dependent pathways in regulating the growth and invasiveness of synovial fibroblasts in rheumatoid arthritis

Cucurbitacin B Alters the Expression of Tumor-Related Genes by Epigenetic Modifications in NSCLC and Inhibits NNK-Induced Lung Tumorigenesis

c-Myc overexpression sensitises colon cancer cells to camptothecin-induced apoptosis

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Myc represses the p21 ^(WAF1/CIP1) promoter and interacts with Sp1/Sp3