Cyclin D1, E2F1 expression levels are associated with characteristics and prognosis of esophageal squamous cell carcinoma

Mega, Seiji; Miyamoto, Masaki; Ebihara, Yuma; Takahashi, Ryo; Hase, Ryunosuke; Li, L.; Shichinohe, Toshiaki; Kawarada, Yo; Uehara, Hirofumi; Kaneko, Hiroyuki; Hashimoto, Hiroyuki; Murakami, Yoshihiro; Itoh, Tomoo; Morikawa, Toshiaki; Kondo, Satoshi

doi:10.1111/j.1442-2050.2005.00463.x

Cited by 35 publications

(25 citation statements)

References 26 publications

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“…However, most data available focus on the function of proliferation-promoting E2F transcription factors, in particular E2F1, in malignant cells. [11][12][13][14][15][16][17] In fact, in non small lung cell carcinoma and esophageal squamous cell carcinoma upregulation of E2F1 was associated with growth advantage and poor clinical outcome. [11][12][13] In small lung cell carcinoma overexpression of E2F1 was linked to deregulation at the transcriptional level, rather than to gene amplification.…”

Section: Discussionmentioning

confidence: 99%

“…[11][12][13][14][15][16][17] In fact, in non small lung cell carcinoma and esophageal squamous cell carcinoma upregulation of E2F1 was associated with growth advantage and poor clinical outcome. [11][12][13] In small lung cell carcinoma overexpression of E2F1 was linked to deregulation at the transcriptional level, rather than to gene amplification. 11 Based on the hypothesis that expression levels of E2F transcripts are tissue-specific and functions of distinct E2F transcription factors could vary among cell types, 5 this study investigated the whole set of E2Fs in various ovarian cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

“…Although most of these alterations associated with malignant disease were found in upstream components of the RB pathway, there is growing evidence that deregulation of E2F transcription factors plays a causative role in human tumors. [11][12][13][14][15][16][17] However, no data are available on the role of E2F in ovarian cancer biology.…”

Section: Introductionmentioning

confidence: 99%

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Heterogeneous cross-talk of E2F family members is crucially involved in growth modulatory effects of interferon-γ and EGF

Reimer

Sadr²,

Wiedemair³

et al. 2006

Cancer Biology & Therapy

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There is growing evidence that deregulation of E2F transcription factors is causatively involved in the patho-physiology of various tumors. However, no data on the role of E2F family members in tumor biology of ovarian cancer are available. We here describe an expression study of all known E2F transcription factors and their coactivators DP-1 and DP-2 in various human ovarian cancer cell lines and the breast cancer cell line T47D and their involvement in pathways affected by interferon-γ and EGF. A significant overexpression of the proliferation-promoting E2F1 and especially E2F2 points to a pivotal role in modulating the uncontrolled proliferation in ovarian cancer cells. Of special note is the fact that interferon-γ treatment did not only caused a reduction of the proliferation-promoting transcription factors E2F1 and E2F2, but also increased the inhibiting transcription factors E2F4 and E2F5, thus underlining the importance of an E2F cross-talk in the anti-proliferative function of interferon-γ. Moreover, an increase in DP-1 and E2F3 is probably involved in the proliferation-enhancing effect of EGF. Our study provides a new insight in the crucial role of E2F cross-talk, especially the role of the inhibiting transcription factors E2F4 and E2F5, in the tumor biology of cancer and its possible usefulness as targets in anti-cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Heterogeneous cross-talk of E2F family members is crucially involved in growth modulatory effects of interferon-γ and EGF

Reimer

Sadr²,

Wiedemair³

et al. 2006

Cancer Biology & Therapy

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“…Considering that cell cycle proteins are critical to regulating cell viability, and cyclin D1 overexpression is significantly associated with poor outcome in esophagus squamous cell carcinoma, 18 we next determined whether S6 or S6K1 affects the expression of cell cycle regulators in G1/S phase transition. Depletion of S6 or S6K1 resulted in a sharp decrease in cyclin D and cdk 2 levels, whereas levels of p21 and p27, which are cyclin-dependent kinase 4/6 inhibitors, were increased, indicating that both S6 and S6K1 regulate cell cycle progression of TE8 and TE10 esophageal cancer cells (Figure 3b and Supplementary Figure S2b).…”

Section: Depletion Of S6 or S6k1 Attenuates Viability Of Esophageal Cmentioning

confidence: 99%

Prognostic significance and function of phosphorylated ribosomal protein S6 in esophageal squamous cell carcinoma

et al. 2013

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Ribosomal protein S6 is a key regulator of 40S ribosome biogenesis, and its phosphorylation is closely related to cell growth capacity. However, as a downstream target of S6 kinases, the clinical significance and the roles of S6 and S6 phosphorylation in cell viability and motility of esophageal squamous cell carcinoma remain unclear. Here, we show that high level of phosphorylated-ribosomal protein S6 (p-S6) (immunohistochemistry score Z5) and an increased ratio of p-S6/S6 (immunohistochemistry score Z0.75) were significantly associated with shortened disease-free survival in patients with esophageal squamous cell carcinoma in univariate analysis (P ¼ 0.049 and Po0.001, respectively). After adjusting for age, tumor-nodes-metastasis stage, chemotherapy, and radiation therapy in multivariate analysis, both p-S6 (hazard ratio 2.21, P ¼ 0.005) and p-S6/S6 (hazard ratio 2.40, Po0.001) remained independent adverse prognostic factors. In addition, S6 and S6 kinase 1 knockdown resulted in attenuation of viability by suppressing cyclin D1 expression in esophageal cancer cells. Furthermore, depletion of S6 and S6 kinase 1 resulted in a reduction in esophageal cancer cell migration and invasion. This was paralleled by a reduction in focal adhesion and by suppression of extracellular signal-regulated kinase and c-jun N-terminal kinase phosphorylation, which control cell motility. Collectively, these findings suggest that p-S6 and the ratio of p-S6/S6 are closely relevant to tumor progression and have prognostic significance in esophageal squamous cell carcinoma. Modern Pathology (2013) 26, 327-335; doi:10.1038/modpathol.2012.161; published online 21 September 2012Keywords: esophagus squamous cell carcinoma; phosphorylation; S6 Esophageal squamous cell carcinoma is one of the most aggressive malignant tumors of the gastrointestinal tract, and has a high mortality rate. 1 The prognosis of esophagus squamous cell carcinoma is poor due to a high incidence of metastasis to lymph nodes, liver, and lung. 1 Despite the development of multimodal therapies including surgery, chemotherapy, radiotherapy, and chemo-radiotherapy, the 5-year survival rate of patients remains in the range of 10 to 25%, 1 underscoring the need for identifying the signaling pathways and downstream targets that lead to esophageal cancer progression and metastasis. 2,3 Recently, the mammalian target of rapamycin (mTOR)-S6 kinase (S6K1) signaling pathway-has emerged as a critical regulator of cellular metabolism, proliferation, and survival in response to growth factor and nutrient availability. [4][5][6][7] Upon growth factor stimulation, mTOR-dependent activation of S6K1 induces phosphorylation of S6, the 40S ribosomal protein at Ser235, Ser236, Ser240, Ser244, and Ser247. 8,9 The importance of S6 phosphorylation is underscored by the finding that mouse embryonic fibroblasts from S6 knock-in mice in which all phosphorylatable serine residues in S6 are substituted by alanines exhibit small cell size, 10 indicating the potential role of S6 phosphorylation in r...

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“…In ESCC cells overexpressing active Notch1, we observed down-regulation of cyclin D1, cyclin E and CDK2, which were considered to be correlated with the altered cell cycle distribution phenotype and growth suppression, also, cell numbers at G 0 /G 1 phase in EC9706 cells transfected with pcNICD markedly increased compared to that in EC9706 cells untreated or transfected with pcDNA3.1, suggesting the proliferation of ESCC cells was suppressed due to the expression changes of cell cycle protein, cyclin D1, cyclin E and CDK2. In human ESCC tissues, increased expression level of cyclin D1 speeded the progress of ESCC and led to poor prognosis (32). It has been reported that overexpression of cyclin E was a general phenomenon associated with oncogenesis of breast cancer (33).…”

Section: Discussionmentioning

confidence: 99%

An activated Notch1 signaling pathway inhibits cell proliferation and induces apoptosis in human esophageal squamous cell carcinoma cell line EC9706

Liu²,

Xue³

et al. 2008

Int J Oncol

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Abstract. Previous studies have demonstrated that Notch1 signaling pathway plays a major role in maintaining the balance of cell proliferation, differentiation and apoptosis, and is closely associated with tumorigenesis. However, roles of Notch1 signaling pathway in esophageal squamous cell carcinoma (ESCC), which is a common cause of mortality in China, remain poorly understood. Therefore, a novel strategy for seeking a rational molecular therapeutic target for ESCC is urgently needed. The purpose of this study is to examine the effect of the active Notch1 signaling pathway on the proliferation and apoptosis of ESCC cells and to investigate the underlying molecular mechanisms in carcinogenesis of the esophagus. The results revealed that a constitutively activated Notch1 signaling pathway was observed in ESCC cell line EC9706, through a pcNICD vector mediated expression system. Clearly, the activated Notch1 signaling pathway gave rise to proliferation suppression of the cells, accompanied with a cell cycle inhibition at the G 0 /G 1 phase and apoptosis. In contrast to the expression of CDK2, cyclin D1 and cyclin E observed in EC9706 cells untreated and transfected with pcDNA3.1, there was a markedly decrease in the cells stably expressing Notch1 NICD. Up-and down-regulations of GSK3ß and ß-catenin, respectively, indicated that Notch1 inhibited proliferation and induced apoptosis of EC9706 cells through Wnt-mediated signaling pathway. These findings suggest that Notch1 signaling pathway may participate in carcinogenesis of the esophagus.

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Cyclin D1, E2F1 expression levels are associated with characteristics and prognosis of esophageal squamous cell carcinoma

Cited by 35 publications

References 26 publications

Heterogeneous cross-talk of E2F family members is crucially involved in growth modulatory effects of interferon-γ and EGF

Heterogeneous cross-talk of E2F family members is crucially involved in growth modulatory effects of interferon-γ and EGF

Prognostic significance and function of phosphorylated ribosomal protein S6 in esophageal squamous cell carcinoma

An activated Notch1 signaling pathway inhibits cell proliferation and induces apoptosis in human esophageal squamous cell carcinoma cell line EC9706

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