STAT3 is a potential modulator of HIF‐1‐mediated VEGF expression in human renal carcinoma cells

Jung, Jae-Chul; Lee, Hyun Gyu; Cho, Ik Hyun; Chung, Doo Hyun; Yoon, Sunhee; Yang, Young Mok; Lee, Sang Eun; Choi, Syngjoo; Park, Jong-Wan; Ye, Sang‐Kyu; Chung, Myung‐Hee

doi:10.1096/fj.04-3099fje

Cited by 387 publications

(352 citation statements)

References 32 publications

Supporting

Mentioning

317

Contrasting

Unclassified

Order By: Relevance

“…The p300/CBP, which is known to be a histone acetyltransferase, is a major binding partner of HIF-1a in enhancing HIF-1a-dependent transcriptional activity (Ema et al, 1999). In addition, it functions as a linker protein between HIF-1a and signal and transducer of transcription 3, another transcriptional regulator of VEGF (Jung et al, 2005). FOXO3a is another key regulator of HIF-1a transcriptional activity.…”

Section: Discussionmentioning

confidence: 99%

Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway

et al. 2011

View full text Add to dashboard Cite

Mel-18 has been implicated in several processes in tumor progression, in which the Akt pathway is involved as an important key molecular event. However, the function of Mel-18 in human cancers has not been fully established yet. Here, we examined the effect of Mel-18 on tumor angiogenesis in human breast cancer, and found that Mel-18 was a novel regulator of HIF-1a. Mel-18 negatively regulated the HIF-1a expression and its target gene VEGF transcription during both normoxia and hypoxia. We demonstrated that Mel-18 regulated the HIF-1a expression and activity via the PI3K/Akt pathway. Loss of Mel-18 downregulated Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression, consequently activating the PI3K/Akt/MDM2 pathway, and leading to an increase of HIF-1a protein level. Mel-18 modulated the HIF-1a transcriptional activity via regulating the cytoplasmic retention of FOXO3a, a downstream effector of Akt, and recruitment of HIF-1a/CBP complex to the VEGF promoter. Furthermore, our data shows that Mel-18 blocked tumor angiogenesis both in vitro and in vivo. Mel-18 overexpression inhibited in vitro tube formation in human umbilical endothelial cells (HUVECs). Xenografts in NOD/SCID mice derived from stably Mel-18 knocked down MCF7 human breast cancer cells showed increased tumor volume, microvessel density, and phospho-Akt and HIF-1a expression levels. In conclusion, our findings provide that Mel-18 is a novel regulator of tumor angiogenesis through regulating HIF-1a and its target VEGF expressions mediated by the PTEN/PI3K/Akt pathway, suggesting a new tumor-suppressive role of Mel-18 in human breast cancer.

show abstract

Section: Discussionmentioning

confidence: 99%

Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Cells were fixed with formaldehyde, and soluble chromatin samples were immunoprecipitated with anti-ARD1, anti-h-catenin, anti-TCF4, or preimmune serum at 4jC overnight (14). DNA isolated from immunoprecipitated material was amplified by semiquantitative PCR with [a-32 P]dCTP.…”

Section: Cancer Res 2006; 66: (22) November 15 2006mentioning

confidence: 99%

Human Arrest Defective 1 Acetylates and Activates β-Catenin, Promoting Lung Cancer Cell Proliferation

Lim¹,

Park²,

2006

View full text Add to dashboard Cite

Arrest defective 1 (ARD1), an acetyltransferase, is essential for the yeast life cycle. Although its human homologue (hARD1) has been identified, its biological functions in human cells remain unclear. In the present study, we examined the biological function of hARD1. In H1299 and A549 lung cancer cells, hARD1-silencing RNA inhibited cell proliferation and induced G 1 arrest. Cyclin D1 was also found to be downregulated in these growth-arrested cells, and the ectopic expression of cyclin D1 rescued cell growth. hARD1 knockdown repressed the promoter activity of the cyclin D1 gene, which inhibited the transcription of cyclin D1. Moreover, hARD1 knockdown reduced the binding of B-catenin/TCF4 transcription factor to cyclin D1 promoter and repressed its transcriptional activity. Inversely, hARD1 expression increased the transcriptional activity of B-catenin. Both endogenous and ectopically expressed hARD1 was coimmunoprecipitated with B-catenin. hARD1 knockdown did not affect B-catenin expression or degradation but noticeably reduced acetylated B-catenin. The B-catenin binding and acetylation by hARD1 were observed in vitro. Therefore, it is suggested that hARD1 participates in proliferation of lung cancer cells via the activation of

show abstract

“…It is known that hypoxia-inducible factor 1 (HIF-1) drives much of hypoxic gene activation and interacts with histone acetyltransferases p300, CBP and SRC-1 [4]. Although the interaction between HIF-1 and CBP/p300 is critical for the activation of a large percentage of hypoxia-inducible genes [5], there are few determinations of histone acetylation levels at the promoters of hypoxia-responsive genes [6]. Additionally, the variety of histone modifications investigated globally and at the promoters of hypoxia-responsive genes is even more limited.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia induces a novel signature of chromatin modifications and global repression of transcription

Johnson¹,

Denko²,

Barton³

2008

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

235

207

View full text Add to dashboard Cite

Tumor cells respond to the harsh hypoxic microenvironment, in part, by transcriptional regulation of specific target genes. We found that hypoxia-mediated activation of selected genes occurs amidst widespread repression of transcription that is neither cell type-specific nor HIF-1-dependent. Despite overall repression, hypoxia induces a pool of histone modifications typically associated with transcriptional activation or repression. Chromatin immunoprecipitation analyses showed that this global mixture of hypoxia-modified histones is sorted in a gene-specific manner to correlate with transcriptional response to hypoxia. Exceptions to this were unexpected increases in H3K4me3 levels, typically associated with transcriptional activation, and decreased H3K27me3 levels, generally a marker of transcriptional silencing, at core promoters of both hypoxia-activated andrepressed genes. These data suggest that a novel signature of chromatin modifications is induced under hypoxic stress, which may play a role in gene regulatory switches active in proliferating tumor cells undergoing cycles of hypoxia and reoxygenation.

show abstract

STAT3 is a potential modulator of HIF‐1‐mediated VEGF expression in human renal carcinoma cells

Cited by 387 publications

References 32 publications

Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway

Loss of Mel-18 induces tumor angiogenesis through enhancing the activity and expression of HIF-1α mediated by the PTEN/PI3K/Akt pathway

Human Arrest Defective 1 Acetylates and Activates β-Catenin, Promoting Lung Cancer Cell Proliferation

Hypoxia induces a novel signature of chromatin modifications and global repression of transcription

Contact Info

Product

Resources

About