Overexpression of E2F1 associated with LOH at RB locus and hyperphosphorylation of RB in non-small cell lung carcinoma

Imai, Miwa; Oda, Yoshio; Oda, Makoto; Nakanishi, Isao; Kawahara, Ei

doi:10.1007/s00432-003-0538-3

Cited by 30 publications

(20 citation statements)

References 30 publications

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“…68 We previously showed that E2F1 is overexpressed in SCLC while it is undetectable in NSCLC as compared to corresponding normal lung, thereby identifying a differential pattern of E2F1 protein expression in lung tumors. 69 By contrast, other studies have reported amplification of the E2F1 gene locus at 20q11.2, 70 as well as increased E2F1 protein level in NSCLC, [71][72][73][74] and have shown that E2F1 is an adverse prognostic factor in these tumors. 71 The reasons of such discrepancies remain unknown.…”

Section: Alteration Of the Components Of G 2 And M Phases In Lung Tumorsmentioning

confidence: 72%

“…72 Amplification of the E2F2 gene locus at 1p36 has also been observed in SCLC 75 and increased expression of E2F3 protein has been found in NSCLC and SCLC. 74 Overall, these studies indicate that E2F factors likely contribute to lung carcinogenesis. However, as E2Fs and notably E2F1 have multiple biological functions, it remains to determine whether each protein contributes to lung tumorigenesis only through deregulation of cell cycle progression, or extands beyond the framework of RB and cell cycle control.…”

Section: Alteration Of the Components Of G 2 And M Phases In Lung Tumorsmentioning

confidence: 99%

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Role of cell cycle regulators in lung carcinogenesis

Eymin

Gazzéri

2010

Cell Adhesion & Migration

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Section: Alteration Of the Components Of G 2 And M Phases In Lung Tumorsmentioning

confidence: 72%

Section: Alteration Of the Components Of G 2 And M Phases In Lung Tumorsmentioning

confidence: 99%

Role of cell cycle regulators in lung carcinogenesis

Eymin

Gazzéri

2010

Cell Adhesion & Migration

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“…In previous studies, E2F1 was shown to promote breast cancer cell and hepatocarcinoma cell proliferation, and conferred antiestrogen resistance to breast cancer cells (Arakawa et al, 2004;Louie et al, 2004). Transgenic models with E2F1 overexpression (Lee et al, 2004) and clinical data from patients with different types of cancer (Gorgoulis et al, 2002;Yamazaki et al, 2003;Imai et al, 2004;Lee et al, 2004;Onda et al, 2004) have further supported the role of E2F1 in oncogenesis. Under normal circumstances, E2F1 gene expression is tightly regulated, and its protein product is rapidly degraded.…”

Section: Discussionmentioning

confidence: 94%

Stabilization of E2F1 protein by MDM2 through the E2F1 ubiquitination pathway

et al. 2005

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Although previous studies suggested that the tumorigenicity of mouse double minute 2 (MDM2) was due to its negative regulation of p53, the p53-independent interactions may be equally as important. During recent studies utilizing MDM2 inhibitors, we noted that E2F transcription factor 1 (E2F1) was downregulated upon inhibition of MDM2, regardless of the p53 status of the cancer. The present study investigated the mechanisms responsible for the MDM2-mediated increase in E2F1 expression. MDM2 prolongs the half-life of the E2F1 protein by inhibiting its ubiquitination. MDM2 displaces SCF SKP2 , the E2F1 E3 ligase. Direct binding between MDM2 and E2F1 is necessary for the negative effects of MDM2 on E2F1 ubiquitination, and deletion of the MDM2 nuclear localization signal does not result in loss of the ability to increase the E2F1 protein level. The downregulation of E2F1 upon MDM2 inhibition was not due to either pRB or p14Arf . In addition, E2F1 was responsible for at least part of the inhibition of cell proliferation induced by MDM2 knockdown. In conclusion, the present study provides evidence that stabilization of the E2F1 protein is likely another p53-independent component of MDM2-mediated tumorigenesis. More knowledge about the MDM2-E2F1 interaction may be helpful in developing novel anticancer therapies.

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“…The main substrates of CDK activation are the Rb protein family (pRb, p107, and p103) and E2F (Imai et al, 2004). Li et al explored the role of antisense RNA gene therapy in targeting cyclin D1 in lung cancer, and they found that knockingdown cyclin D1 can induce apoptosis in A549 cells, which may be associated with the reduced expression of intracellular pRb, E2F1, VEGF, MMP-2, and MMP-9 (Li et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

JNK pathway and relative transcriptional factor were involved in ginsenoside Rh2-mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells

et al. 2016

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ABSTRACT. Ginsenoside Rh2 has been shown to have an antitumor effect on a wide range of cancers. A previous study has shown that ginsenoside Rh2 can inhibit the proliferation of the human lung adenocarcinoma A549 cell line in a dose-dependent manner by activating caspase-8/3 activity to promote apoptosis. However, the association of the JNK signaling pathways and transcription factors with ginsenoside Rh2 in the suppression of non-small cell lung cancer has not yet been reported. In this study, we found that ginsenoside Rh2 can activate the JNK/MAPKs signaling pathway and increase the phosphorylation and transcriptional activity of the transcription factors AP-1 and ATF2. Ginsenoside Rh2 also reduced the expression of transcription factors E2F1 and c-Myc. Furthermore, ginsenoside Rh2 affected the expression levels of cyclin D1 and the CDK4 protein, which are key regulatory factors of the G1/S cyclin-dependent kinase. The anti-proliferative and induced apoptotic effects of ginsenoside Rh2 on A549 cell provide evidence to support the application of traditional Chinese medicine to lung cancer treatment.

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Overexpression of E2F1 associated with LOH at RB locus and hyperphosphorylation of RB in non-small cell lung carcinoma

Abstract: Our results suggest that overexpression of E2F1, induced both by LOH at the RB locus and anomalous phosphorylation of the RB protein, is involved in the development of non-small cell lung carcinoma.

Cited by 30 publications

References 30 publications

Role of cell cycle regulators in lung carcinogenesis

Role of cell cycle regulators in lung carcinogenesis

Stabilization of E2F1 protein by MDM2 through the E2F1 ubiquitination pathway

JNK pathway and relative transcriptional factor were involved in ginsenoside Rh2-mediated G1 growth arrest and apoptosis in human lung adenocarcinoma A549 cells

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