MZF1 possesses a repressively regulatory function in ERCC1 expression

Yan, Qing-Wu; Reed, Eddie; Zhong, Xiaosong; Thornton, Keith; Guo, Yi; Yu, Jing

doi:10.1016/j.bcp.2005.12.015

Cited by 41 publications

(33 citation statements)

References 31 publications

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“…This region is also implicated in the basal expression of ERCC1 as a high drop was observed between the two constructs. A myeloid zinc finger 1 (MZF1) transcription factor is also localized at position À509 to À503 but does not seem to be implicated in this decrease contrary to the other one at position À324 to 298 recently reported to repressively regulate ERCC1 expression upon cisplatin exposure in ovarian cancer cells (30). Moreover, the decrease was much higher in hepatic cells than in HeLa cells (data not shown); this could be due to the presence of the hepatospecific sequence HNF1 at position À584/À591.…”

Section: Resultsmentioning

confidence: 78%

GATA-1 Is Essential in EGF-Mediated Induction of Nucleotide Excision Repair Activity and ERCC1 Expression through ERK2 in Human Hepatoma Cells

et al. 2007

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The nucleotide excision repair (NER) pathway and its leading gene excision-repair cross-complementary 1 (ERCC1) have been shown to be up-regulated in hepatocellular carcinomas even in the absence of treatment with chemotherapeutics. The aim of this study was to determine the mechanism involved in NER regulation during the liver cell growth observed in hepatocellular carcinoma. Both NER activity and ERCC1 expression were increased after exposure to the epidermal growth factor (EGF) in cultured normal and tumoral human hepatocytes. These increases correlated with the activation of the kinase signaling pathway mitogen-activated protein/extracellular signalregulated kinase (ERK) kinase (MEK)/ERK that is known to be a key regulator in the G 1 phase of the hepatocyte cell cycle. Moreover, EGF-mediated activation of ERCC1 was specifically inhibited by either the addition of U0126, a MEK/ERK inhibitor or small interfering RNA-mediated knockdown of ERK2. Basal expression of ERCC1 was decreased in the presence of the phosphoinositide-3-kinase (PI3K) inhibitor and small hairpin RNA (shRNA) against the PI3K pathway kinase FKBP12-rapamycin-associated protein or mammalian target of rapamycin. Transient transfection of human hepatocytes with constructs containing different sizes of the 5 ¶-flanking region of the ERCC1 gene upstream of the luciferase reporter gene showed an increase in luciferase activity in EGF-treated cells, which correlated with the presence of the nuclear transcription factor GATA-1 recognition sequence. The recruitment of GATA-1 was confirmed by chromatin immunoprecipitation assay. In conclusion, these results represent the first demonstration of an up-regulation of NER and ERCC1 in EGFstimulated proliferating hepatocytes. The transcription factor GATA-1 plays an essential role in the induction of ERCC1 through the mitogen-activated protein kinase (MAPK) pathway, whereas the PI3K signaling pathway contributes to ERCC1 basal expression. [Cancer Res 2007;67(5):2114-23]

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Section: Resultsmentioning

confidence: 78%

GATA-1 Is Essential in EGF-Mediated Induction of Nucleotide Excision Repair Activity and ERCC1 Expression through ERK2 in Human Hepatoma Cells

et al. 2007

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“…35). MZF1 is upregulated in those settings in which AP1 is downregulated; and, MZF1 is downregulated when AP1 is upregulated.…”

Section: The Control Of Dna Damage and Repairmentioning

confidence: 94%

DNA Damage and Repair in Translational Oncology: An Overview

Reed

2010

Clinical Cancer Research

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Unknown to early investigators, DNA damage and repair has been a major focus of anticancer therapy from the beginning of clinical oncology. From the early days of using x-irradiation, to the development of nitrogen mustard analogs, to today's more sophisticated approaches, DNA damage and repair has strongly impacted our ability to successfully treat human malignancy. This area of basic, translational, and clinical science is very broad. The traditional focus of DNA damage and repair has been on diseases such as Xeroderma pigmentosum, and attempting to understand the basic molecular mechanisms of DNA repair processes. It is only recently that we have begun to appreciate how we might modulate these processes to improve our ability to advance cancer care. No fewer than 10 separate DNA repair processes are operative in higher organisms, and the total number of separable processes could be substantially higher. Some of our most useful clinical agents depend on causing DNA damage that is repaired by nucleotide excision repair. X-irradiation induces damage that is mostly repaired by base excision repair and double-strand break repair. We are now learning how to modulate select DNA repair pathways to benefit patients with breast cancer and other malignancies. Clin Cancer Res; 16(18); 4511-6. ©2010 AACR.DNA damage and repair is a subject of enormous breadth and depth. We commonly underestimate the importance of DNA damage and repair in the successful treatment of cancer, and, in general, also underestimate the overall importance of DNA damage and repair in oncology. For example, the most widely used class of anticancer compounds is the platinum series of agents, cisplatin, carboplatin, and oxaliplatin (1, 2). One or more of these agents represents the cornerstone of the current standard of care in the vast majority of solid tumors, including lung cancer, head and neck cancers, upper and lower gastrointestinal malignancies, genitourinary malignancies, and solid tumors of childhood. Alkylating agents have long been the backbone of treatment regimens for lymphomas, and other hematologic malignancies. Radiation therapy is critically important to cure, in a large range of early stage diseases. Despite its importance, much less is written about DNA repair than many of the other common subcellular processes that govern cancer causation and cancer treatment.DNA damage occurs in many forms, as a result of a range of many different types of exposures. Similarly, DNA repair is executed in a variety of ways; these processes having evolved over many millions of years, with the earliest of versions seen in the most rudimentary unicellular life forms. At a minimum, most would agree that the following are distinct pathways of DNA repair that occur in higher organisms: nucleotide excision repair (NER), base excision repair (BER), mismatch repair (MMR), doublestrand break repair (DSBR), direct reversal, translesion synthesis, homologous recombination, and nonhomologous end-joining.In this issue of Clinical Cancer Research, we touc...

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“…3C, up arrows). The MZF1 binding motif of the ERCC1 promoter (−324/−298 bp) was used as a positive control (41), which showed a significant increase in MZF1 binding with MZF1-overexpressing nuclear extracts of HeLa cells (Supplementary Fig. S2B).…”

Section: Mzf1 Nuclear Proteins Bind To the Axl Promotermentioning

confidence: 99%

Myeloid Zinc Finger 1 Induces Migration, Invasion, and In vivo Metastasis through Axl Gene Expression in Solid Cancer

Mudduluru

Vajkoczy

Allgayer

2010

Molecular Cancer Research

118

129

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Myeloid zinc finger 1 (MZF1) is a member of the SCAN domain family transcription factors that form dimers through their highly conserved SCAN motifs. Silencing of MZF1 inhibits cell proliferation, and abnormal expression of MZF1 results in cancer development. However, a potential role of MZF1 in metastasis remains unclear. Axl is a receptor tyrosine kinase and was first identified as a transforming gene in chronic myeloid leukemia. Axl overexpression induces proliferation, migration, and invasion and is highly expressed in different human cancers. In this study, we show that overexpression of MZF1 induces migration and invasion in colorectal (Rko, SW480) and cervical (HeLa) cancer cells. In addition, we show that MZF1 binds to the Axl promoter, transactivates promoter activity, and enhances Axl-mRNA and protein expression in a dose-dependent manner. In vitro, sh-RNA knockdown of Axl reduced MZF1-induced migration and invasion in HeLa and Rko cells (P = 0.05). Additionally, Rko cells overexpressing MZF1 showed increased tumor formation and liver metastasis in the chicken-embryo-metastasis assay in vivo. Furthermore, the expression of MZF1 and Axl was significantly higher in resected colorectal tumors compared with corresponding normal tissues (P = 0.02; P = 0.05), and MZF1 expression was positively correlated with Axl gene expression in tumor tissues (P < 0.01). Taken together, this is the first study to show that MZF1 induces invasion and in vivo metastasis in colorectal and cervical cancer, at least in part by regulating Axl gene expression. Mol Cancer Res; 8(2); 159-69. ©2010 AACR.

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MZF1 possesses a repressively regulatory function in ERCC1 expression

Cited by 41 publications

References 31 publications

GATA-1 Is Essential in EGF-Mediated Induction of Nucleotide Excision Repair Activity and ERCC1 Expression through ERK2 in Human Hepatoma Cells

GATA-1 Is Essential in EGF-Mediated Induction of Nucleotide Excision Repair Activity and ERCC1 Expression through ERK2 in Human Hepatoma Cells

DNA Damage and Repair in Translational Oncology: An Overview

Myeloid Zinc Finger 1 Induces Migration, Invasion, and In vivo Metastasis through Axl Gene Expression in Solid Cancer

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