Involvement of aberrant DNA methylation on reduced expression of lysophosphatidic acid receptor-1 gene in rat tumor cell lines

Tsujiuchi, Toshifumi; Shimizu, Kyoko; Onishi, Mariko; Sugata, Eriko; Fujii, Hiromasa; Mori, Toshio; Honoki, Kanya; Fukushima, Nobuyuki

doi:10.1016/j.bbrc.2006.08.159

Cited by 23 publications

(20 citation statements)

References 27 publications

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“…Semi-quantitative RT-PCR analysis was performed as described previously [16,17] . Primer pairs used in this study were as follows: for mouse LPA1 (NCBI accession No.…”

Section: Semi-quantitative Rt-pcr Amplification For the Lpa1 And Lpa3mentioning

confidence: 99%

“…For each gene, multiple cycles of PCR amplification were tested and the most appropriate cycle number was determined. The amplified products were then separated on 2% agarose gels containing 0.05 g/ml ethidium bromide [16,17] .…”

Section: Semi-quantitative Rt-pcr Amplification For the Lpa1 And Lpa3mentioning

confidence: 99%

“…Our recent reports have indicated that distinct expression patterns of LPA receptor genes occur in human colon cancer cells [16] . In rodents, loss of LPA1 expression due to its aberrant DNA methylation was shown in rat tumor cells [17] . On the other hand, mutations of LPA receptor genes have also been detected in human and rodents tumors [16,18,19] .…”

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confidence: 99%

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Different Expressions and DNA Methylation Patterns of Lysophosphatidic Acid Receptor Genes in Mouse Tumor Cells

Okabe

Hayashi²,

Wakabayashi³

et al. 2010

Pathobiology

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Objective: Lysophosphatidic acid (LPA) receptors act as several biological effectors through LPA, which is a bioactive phospholipid. Recently, aberrant expressions of LPA receptor genes due to DNA methylation have been detected in several tumor cells. In this study, we measured expression levels and DNA methylation status of LPA receptor genes in mouse tumor cells, LL/2 lung carcinoma, B16F0 melanoma, FM3A mammary carcinoma and L1210 leukemia cells, compared with normal tissues. Methods: Total RNAs were extracted and RT-PCR analysis was performed. For DNA methylation status, bisulfite sequencing analysis was carried out, comparing outcomes with other tumor cells and normal tissues. Results: The expressions of LPA1 gene were shown in LL/2, but not in B16F0, FM3A and L1210 cells. While the LPA2 gene was expressed in all 4 tumor cells, the LPA3 gene was unexpressed in them. The LPA1 and LPA3 unexpressed cells were highly methylated, although normal tissues were all unmethylated. The DNA methylation status was correlated with gene expression levels in cancer cells. Conclusion: The present results demonstrate that DNA methylation patterns of LPA receptor genes are dependent on cancer cell types, suggesting that LPA receptors may be new molecular targets for therapeutic approaches and chemoprevention.

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“…Semi-quantitative RT-PCR analysis was performed as described previously [16,17] . Primer pairs used in this study were as follows: for mouse LPA1 (NCBI accession No.…”

Section: Semi-quantitative Rt-pcr Amplification For the Lpa1 And Lpa3mentioning

confidence: 99%

Section: Semi-quantitative Rt-pcr Amplification For the Lpa1 And Lpa3mentioning

confidence: 99%

See 1 more Smart Citation

Different Expressions and DNA Methylation Patterns of Lysophosphatidic Acid Receptor Genes in Mouse Tumor Cells

Okabe

Hayashi²,

Wakabayashi³

et al. 2010

Pathobiology

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“…While these cells express only selective LPA receptors, they still maintain the genes for others. A recent publication indicated that the absence of the LPA1 receptor expression in both B103 and RH7777 rat cell lines was the result of hypermethylation in the 5′ upstream region of the gene since treatment with a DNA methyltransferase inhibitor lead to re-expression of the LPA1 receptor gene and protein [30]. Whether this occurs in other cell types and human cancers is currently unknown.…”

Section: The Lpa1 Receptor As a Negative Regulator Of Ovarian Tumor Pmentioning

confidence: 99%

Sharpening the edges of understanding the structure/function of the LPA1 receptor: Expression in cancer and mechanisms of regulation☆

Murph

2008

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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Since the molecular cloning of the vzg-1/Edg-2/LPA1 gene, studies have attempted to characterize LPA1 receptor functionality into a single categorical role, different from the other Edg-family LPA receptors. The desire to categorize LPA1 function has highlighted its complexity and demonstrated that the LPA1 receptor does not have one absolute function throughout every system. The central nervous system is highly enriched in the LPA1 receptor, suggesting an integral role in neuronal processes. Metastatic and invasive breast cancer also appears to have LPA-mediated LPA1 receptor functions that enhance phenotypes associated with tumorigenesis. LPA1 possesses a number of motifs conserved among G protein-coupled receptors (GPCRs): a DRY-like motif, a PDZ domain, Ser/Thr predicted sites of phosphorylation, a dileucine motif, double cysteines in the tail and conserved residues that stabilize structure and determine ligand binding. The third intracellular loop of the LPA1 receptor may be the crux of receptor signaling and attenuation with phosphorylation of Thr-236 potentially a key determinant of basal LPA1 signaling. Mutagenesis data supports the notion that Thr-236 regulates this process since mutating Thr-236 to Ala-236 increased basal and LPAmediated serum response factor (SRF) signaling activity and Lys-236 further increased this basal signaling. Here we describe progress on defining the major functions of the LPA1 receptor, discuss a context dependent dualistic role as both a negative regulator in cancer and a proto-oncogene, outline its structural components at the molecular amino-acid level and present mutagenesis data on the third intracellular loop of the receptor.

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“…Certain cancer cell types methylate the BubR1, 7-dehydrocholesterol reductase (Dhcr7), aquaporin-5 (AQP5), RUNX3, lysophosphatidic acid receptor-1 (lpa1), galectin-3, CDX1, MUC5B, PDZ-LIM domain-containing protein 2 (PDLIM2), LOT1 (PLAGL1/ZAC1), TNFSF7 (CD70) genes, leading to their transcriptional suppression DNA hypomethylation at CpG islands within the promoters (Abdollahi et al, 2003;Ahmed et al, 2007;Kim et al, 2005;Motegi et al, 2005;Park et al, 2005;Perrais et al, 2001;Qu et al, 2010;Suh et al, 2002;Tsujiuchi et al, 2006;Yu et al, 2010). The upregulation of galectin-7, CDX4, and urokinase-type plasminogen activator (uPA), and MMP-2 genes in several cancer types including breast cancer, ovarian cancer, and lymphoma cells is mediated by DNA hypomethylation (Chernov et al, 2009;Demers et al, 2009;Guo et al, 2002;Honda et al, 2006;Pakneshan et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Epigenetic Up-Regulation of Leukemia Inhibitory Factor (LIF) Gene During the Progression to Breast Cancer

Shin

Park

Jang

2011

Molecules and Cells

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The interleukin 6 family of cytokines including leukemia inhibitory factor (LIF) regulates the progression of several types of cancer. However, although LIF overexpression during breast cancer progression was observed in our previous report, the molecular mechanisms responsible for this deregulation remain largely unknown. Here we show that LIF expression is epigenetically up-regulated via DNA demethylation and changes in histone methylation status within its promoter region in the isogenic MCF10 model. Bisulfite sequencing revealed the CpG pairs within the promoter region are hypermethylated in normal breast epithelial cells, but extensively demethylated as breast cancer progresses. In agreement with the DNA methylation pattern, our chromatin immunoprecipitation showed that inactive epigenetic marks such as MeCP2 occupancy and histone H3-Lys9-dimethylation significantly decreased during the progression to breast cancer but an active histone mark was increased in an inverse manner. Also, the occupancy of the transcription factor Sp1, which has higher affinity for hypomethylated CpGs, increased. RNAimediated knockdown of LIF expression resulted in a significant reduction of cell growth and colony formation in breast cancer cells, suggesting the potential role of LIF-LIF receptor axis in autocrine stimulation of cancer cells. Collectively, our data suggest that the epigenetic up-regulation of the LIF gene likely play an important role in the development of breast cancer.

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Involvement of aberrant DNA methylation on reduced expression of lysophosphatidic acid receptor-1 gene in rat tumor cell lines

Cited by 23 publications

References 27 publications

Different Expressions and DNA Methylation Patterns of Lysophosphatidic Acid Receptor Genes in Mouse Tumor Cells

Different Expressions and DNA Methylation Patterns of Lysophosphatidic Acid Receptor Genes in Mouse Tumor Cells

Sharpening the edges of understanding the structure/function of the LPA1 receptor: Expression in cancer and mechanisms of regulation☆

Epigenetic Up-Regulation of Leukemia Inhibitory Factor (LIF) Gene During the Progression to Breast Cancer

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