C/EBPα Is Up-regulated in a Subset of Hepatocellular Carcinomas and Plays a Role in Cell Growth and Proliferation

Lu, Guo‐Dong; Leung, Carol Ho-Wing; Yan, Benedict; Tan, Colyn Mui-Yeong; Low, Sie Yieh; Aung, Myat Oo; Salto-Tellez, Manuel; Lim, Seng Gee; Hooi, Shing Chuan

doi:10.1053/j.gastro.2010.03.051

Cited by 43 publications

(43 citation statements)

References 24 publications

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“…Consistent with our findings, recent studies reported that overexpression of C/EBPα occurs in cancer, such as B precursor acute lymphoblastic leukemia (ALL) and a subset of human hepatocellular carcinomas (HCCs) [22,40]. Importantly, C/EBPα induces BCL2 and FLIP gene expression in cooperation with NF-κB p50, allowing cancer cells to escape apoptosis [23].…”

Section: Discussionsupporting

confidence: 90%

HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C/EBPα signaling

Zhao

Coutts

et al. 2013

Retrovirology

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BackgroundHuman T-cell leukemia virus type 1 (HTLV-1) is an oncogenic retrovirus etiologically associated with adult T-cell leukemia (ATL). The HTLV-1 bZIP factor (HBZ), which is encoded by minus strand of provirus, is expressed in all ATL cases and supports the proliferation of ATL cells. However, the precise mechanism of growth promoting activity of HBZ is poorly understood.ResultsIn this study, we showed that HBZ suppressed C/EBPα signaling activation induced by either Tax or C/EBPα. As mechanisms of HBZ-mediated C/EBPα inhibition, we found that HBZ physically interacted with C/EBPα and diminished its DNA binding capacity. Luciferase and immunoprecipitation assays revealed that HBZ repressed C/EBPα activation in a Smad3-dependent manner. In addition, C/EBPα was overexpressed in HTLV-1 infected cell lines and fresh ATL cases. HBZ was able to induce C/EBPα transcription by enhancing its promoter activity. Finally, HBZ selectively modulated the expression of C/EBPα target genes, leading to the impairment of C/EBPα-mediated cell growth suppression.ConclusionHBZ, by suppressing C/EBPα signaling, supports the proliferation of HTLV-1 infected cells, which is thought to be critical for oncogenesis.

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Section: Discussionsupporting

confidence: 90%

HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C/EBPα signaling

Zhao

Coutts

et al. 2013

Retrovirology

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“…Quantitative PCR (qPCR) was carried out using an ABI StepOne Plus system along with ABI Fast SYBR (Applied Biosystems, Carlsbad, CA). Primers for C/EBP␤ were designed across exon boundaries and were previously described (29). Primer pair efficiencies for glyceraldehyde 3-phosphate dehydrogenase (GAPDH), ␤-actin, and C/EBP␤ were validated before analysis for C/EBP␤ expression.…”

Section: Antagomir Derepression Assays and Real-time Quantitative Rt-mentioning

confidence: 99%

A Kaposi's Sarcoma-Associated Herpesvirus-Encoded Ortholog of MicroRNA miR-155 Induces Human Splenic B-Cell Expansion in NOD/LtSz-scid IL2Rγ ^null Mice

Boss

Nadeau

Abbott

et al. 2011

J Virol

112

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“…Similarly, studies on human hepatocellular carcinomas (HCC) [30] showed up-regulation of CEBPA at both mRNA and protein levels. A forced down-regulation of this gene led to reduced colony formation and cell growth.…”

Section: Discussionmentioning

confidence: 99%

The significance of c.690G>T polymorphism (rs34529039) and expression of the CEBPA gene in ovarian cancer outcome

Konopka

Szafron

et al. 2016

Oncotarget

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The CEBPA gene is known to be mutated or abnormally expressed in several cancers. This is the first study assessing the clinical impact of CEBPA gene status and expression on the ovarian cancer outcome. The CEBPA gene sequence was analyzed in 118 ovarian cancer patients (44 platinum/cyclophosphamide (PC)-treated and 74 taxane/platinum (TP)-treated), both in tumors and blood samples, and in blood from 236 healthy women, using PCR-Sanger sequencing and Real-Time quantitative PCR (qPCR)-based genotyping methods, respectively. The CEBPA mRNA level was examined with Reverse Transcription quantitative PCR (RT-qPCR). The results were correlated to different clinicopathological parameters. Thirty of 118 (25.4%) tumors harbored the CEBPA synonymous c.690G>T polymorphism (rs34529039), that we showed to be related to up-regulation of CEBPA mRNA levels (p=0.0059). The presence of the polymorphism was significantly associated with poor prognosis (p=0.005) and poor response to the PC chemotherapy regimen (p=0.024). In accordance, elevated CEBPA mRNA levels negatively affected patient survival (p<0.001) and tumor response to the PC therapy (p=0.014). The rs34529039 SNP did not affect the risk of developing ovarian cancer. This is the first study providing evidence that the c.690G>T, p.(Thr230Thr) (rs34529039) polymorphism of the CEBPA gene, together with up-regulation of its mRNA expression, are negative factors worsening ovarian cancer outcome. Their adverse clinical effect depends on a therapeutic regimen used, which might make them potential prognostic and predictive biomarkers for response to DNA-damaging chemotherapy.

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C/EBPα Is Up-regulated in a Subset of Hepatocellular Carcinomas and Plays a Role in Cell Growth and Proliferation

Cited by 43 publications

References 24 publications

HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C/EBPα signaling

HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C/EBPα signaling

A Kaposi's Sarcoma-Associated Herpesvirus-Encoded Ortholog of MicroRNA miR-155 Induces Human Splenic B-Cell Expansion in NOD/LtSz-scid IL2Rγ ^null Mice

The significance of c.690G>T polymorphism (rs34529039) and expression of the CEBPA gene in ovarian cancer outcome

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C/EBPα Is Up-regulated in a Subset of Hepatocellular Carcinomas and Plays a Role in Cell Growth and Proliferation

Cited by 43 publications

References 24 publications

HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C/EBPα signaling

HTLV-1 bZIP factor supports proliferation of adult T cell leukemia cells through suppression of C/EBPα signaling

A Kaposi's Sarcoma-Associated Herpesvirus-Encoded Ortholog of MicroRNA miR-155 Induces Human Splenic B-Cell Expansion in NOD/LtSz-scid IL2Rγ null Mice

The significance of c.690G>T polymorphism (rs34529039) and expression of the CEBPA gene in ovarian cancer outcome

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Product

Resources

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A Kaposi's Sarcoma-Associated Herpesvirus-Encoded Ortholog of MicroRNA miR-155 Induces Human Splenic B-Cell Expansion in NOD/LtSz-scid IL2Rγ ^null Mice