Transcriptional analysis of the mts1 gene with specific reference to 5' flanking sequences.

Tulchinsky, Eugene; Ford, Heide L.; Крамеров, Д. А.; Reshetnyak, Elena; Grigorian, Mariam; Zain, Sayeeda; Lukanidin, Eugene

doi:10.1073/pnas.89.19.9146

Cited by 26 publications

(32 citation statements)

References 26 publications

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“…Such a mechanism, in this case, might be methylation of the S100A4 (p9Ka) gene, as reported previously for the mouse S100A4 (mts1) gene (11). The results of the present experiments contrast with those previously obtained using metastatic and non-metastatic murine mammary cells in which no evidence of important cisacting regulatory sequences were found in the 5Ј region of the mouse S100A4 (mts1) gene in the region Ϫ41 to Ϫ1,897 upstream of the transcriptional start site (10). One possible explanation for the difference between the results with the rat and mouse S100A4 genes is that in the mouse S100A4 (mts1) gene, any GC-factor-binding sequence might lie further upstream than the 0 to Ϫ1,897 region examined (10).…”

Section: Cell Linecontrasting

confidence: 58%

“…It has been reported that cis-acting elements 5Ј of the region immediately upstream of the TATA box play little or no part in transcription of the mouse S100A4 (mts1) gene (10), but the loss of methylation of DNA may be associated with transcriptional activation of this gene in mice and human lymphoma cells (10,11). Further analysis of the natural mouse gene revealed two elements within the first intron that may be involved in regulating the expression of the S100A4 (mts1) gene in this species (12). The nucleotide sequence of this reported 16-bp 1 protected element is identical in both the mouse and the rat genomes (2,12).…”

mentioning

confidence: 99%

“…Further analysis of the natural mouse gene revealed two elements within the first intron that may be involved in regulating the expression of the S100A4 (mts1) gene in this species (12). The nucleotide sequence of this reported 16-bp 1 protected element is identical in both the mouse and the rat genomes (2,12). However, the expression of the rat S100A4 (p9Ka) transgene under the control of its own promoter in transgenic mice suggests a different pattern of expression between these two species (5).…”

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confidence: 99%

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Transcriptional Down-regulation of the Metastasis-inducing S100A4 (p9Ka) in Benign but Not in Malignant Rat Mammary Epithelial Cells by GC-factor

Chen

Davies

Rudland

et al. 1997

Journal of Biological Chemistry

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The S100-related calcium-binding protein S100A4 (p9Ka) is expressed at a low level in rat mammary epithelial cells from normal mammary gland and benign mammary tumors. In transgenic mice, expressed rat S100A4 transgenes co-operate with the activated c-erbB-2 oncogene, neu, to form metastatic mammary tumors. Elevated levels of S100A4 (p9Ka) in cultured benign rat or mouse mammary epithelial cells are associated with the induction of metastatic capability. A cis-acting sequence related to the consensus recognition sequence of GC-factor, 1,300 base pairs upstream of the start site of transcription of the rat S100A4 gene, acts as a cis-acting inhibitor of transcription of the S100A4 (p9Ka) gene in a low S100A4 (p9Ka)-expressing benign rat mammary epithelial cell line, but not in highly expressing rat mammary epithelial cell lines. There is an inverse relationship between the level of S100A4 (p9Ka) mRNA and the level of GC-factor mRNA in a range of rat mammary cell lines. The results suggest a novel mechanism for regulating the expression of the mRNA encoding an S100 protein.S100A4 (p9Ka) is a member of the S100 family of calciumbinding proteins first identified in a cultured myoepitheliallike cell line, Rama 29 (1). The S100A4 (p9Ka) gene has been isolated and its nucleotide sequence determined (2). Elevation of the level of S100A4 (p9Ka) in benign, non-metastatic rat (3) and mouse (4) cells induces metastatic capability in some of the cells. Although mice containing multiple copies of a rat (5) or mouse (6) S100A4 transgene show no observable phenotype, mice which contain cells that express both the rat S100A4 transgenes and the activated neu oncogene, or mouse S100A4 transgenes in a genetic background that yields primary mammary tumors, succumb to metastatic mammary tumors (6, 7), strongly suggesting that overexpression of S100A4 in mammary tumors can yield the metastatic phenotype. Some rat and mouse cultured mammary epithelial cell lines of high metastatic potential contain elevated levels of S100A4, when compared with their non-metastatic counterparts (8, 9).

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Section: Cell Linecontrasting

confidence: 58%

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confidence: 99%

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confidence: 99%

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Transcriptional Down-regulation of the Metastasis-inducing S100A4 (p9Ka) in Benign but Not in Malignant Rat Mammary Epithelial Cells by GC-factor

Chen

Davies

Rudland

et al. 1997

Journal of Biological Chemistry

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“…Previous studies suggested a possible role of DNA methylation in the control of tissue-specific expression of S100A4. 28 The S100A4 promoter does not contain CpG islands, and CpG sites throughout the gene are sparsely distributed. 28,29 DNA methylationdependent repression of several other genes lacking CpG-rich promoters has been previously described.…”

Section: Methylation Status Of S100a4mentioning

confidence: 99%

“…28 The S100A4 promoter does not contain CpG islands, and CpG sites throughout the gene are sparsely distributed. 28,29 DNA methylationdependent repression of several other genes lacking CpG-rich promoters has been previously described. 30,31 There is a correlation between hypomethylation of the CpG sites in the first intron of S100A4 and gene activation in human lymphoma, 32 colon cancer cell lines, 32,33 and pancreatic cancer cell lines and primary pancreatic ductal adenocarcinomas.…”

Section: Methylation Status Of S100a4mentioning

confidence: 99%

Hypomethylation-induced expression of S100A4 in endometrial carcinoma

et al. 2007

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Expression of various S100 genes has been associated with clinically aggressive subtypes in a variety of different cancers. We hypothesized that S100A4 would be overexpressed in endometrial carcinoma compared to benign endometrium. Quantitative real-time RT-PCR (qRT-PCR) was used to quantify the mRNA level of S100A4 in benign endometrium (n ¼ 19), endometrioid adenocarcinoma (n ¼ 87), and non-endometrioid tumors (n ¼ 21). Immunohistochemistry was used to verify the results of qRT-PCR and to assess protein localization. Possible mechanisms of S100A4 gene regulation were also examined. S100A4 was overexpressed in the grade 3 endometrioid tumors, uterine papillary serous carcinoma, and uterine malignant mixed mü llerian tumor. Expression in grade 1 and grade 2 endometrioid tumors was comparable to that of normal endometrium, which was quite low. Expression was significantly higher in stage III and IV tumors compared with stage I. By immunohistochemistry, S100A4 was expressed in the tumor cell cytoplasm of poorly differentiated tumors, but was not detected in normal endometrial glandular epithelium. In benign endometrium, S100A4 expression was confined to stromal cells. S100A4 was not regulated by estrogen or progesterone, and its expression in tumors was not significantly correlated to estrogen receptor or progesterone receptor content. However, methylation of the S100A4 gene was detected in benign endometrium and grade 1 tumors with low S100A4 expression. In contrast, grade 3 endometrioid tumors with high S100A4 mRNA and protein expression showed no methylation of the gene. These methylation results were verified in endometrial cancer cell lines with differential baseline levels of S100A4 protein. These results suggest that hypomethylation is an important mechanism of regulating the expression of the S100A4 gene. These results support the emerging concept that hypomethylation may play a role in the upregulation of genes during later stages of tumorigenesis. Keywords: endometrial cancer; S100A gene family; S100A4; methylation Endometrial carcinoma is the most common malignant neoplasm of the female genital tract and the fourth most frequently diagnosed cancer in women, following cancers of the breast, lung, and colon. 1 On the basis of histological and clinical features, endometrial carcinoma has been classified into two types. 2-4 Type I tumors (approximately 80% of all endometrial carcinomas) are typically low-grade (grade 1 or grade 2) endometrioid adenocarcinoma, most of which are confined to the uterus and have a favorable prognosis. Type II tumors (approximately 20%) are comprised of uterine papillary serous carcinoma, malignant mixed mü llerian tumors, and clear cell carcinoma. The nature of high-grade (grade 3) endometrioid adenocarcinoma is more controversial, as a subset may behave more like the Type II tumors. Type II cancers are associated with extrauterine spread and carry a high mortality rate. Previous studies have documented interesting molecular differences between endometrioid and nonendometrioid ...

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Modulation of mts1 expression in mouse and human normal and tumor cells

Grigorian¹,

Tulchinsky²,

Burrone³

et al. 1994

Electrophoresis

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The mts1 gene, encoding small Ca(2+)-binding protein of the S100-family, is considered as a gene whose activity correlates with the manifestation of a metastatic phenotype of tumor cells. It was shown before that the mts1 is expressed not only in metastatic tumor cells but also in some normal tissues, namely in so-called "lymphoid" organs: spleen, thymus, bone marrow. In this work we analyzed in more detail the expression of mts1 in human and mouse hematopoietic cells and cell lines. A high level of mts1 RNA was observed in T-lymphocytes, neutrophils, monocytes/macrophages and in corresponding cell lines. Controversially, the mts1 gene was silent in B-lymphocytes as well as in myeloma and erythroleukemia cell lines. The possibility of modulating the mts1 gene expression by the action of different agents was demonstrated. Mitogens, such as lipopolysaccharides (LPS), interferon (IFN gamma), and concanavalin A (Con A), modulate the level of the mts1 gene expression in hematopoietic cells differently. Calcium ionophore, A23187, can also be regarded as a modulator of the mts1 gene expression, since its addition to the cells results in a substantial decrease of the mts1 RNA level. It was shown that the mts1 RNA's half-life is relatively long, more than 24 h. We therefore believe that calcium ionophore can activate some ribonucleases which degrade the mts1 RNA. Cycloheximide prevents the effect of A23187 and stabilizes the mts1 RNA, probably by blocking the synthesis of these nucleases. Thus, the obtained data indicate that the agents which are capable of changing the physiological status of the cells also modulate the mts1 gene expression.

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Transcriptional analysis of the mts1 gene with specific reference to 5' flanking sequences.

Cited by 26 publications

References 26 publications

Transcriptional Down-regulation of the Metastasis-inducing S100A4 (p9Ka) in Benign but Not in Malignant Rat Mammary Epithelial Cells by GC-factor

Transcriptional Down-regulation of the Metastasis-inducing S100A4 (p9Ka) in Benign but Not in Malignant Rat Mammary Epithelial Cells by GC-factor

Hypomethylation-induced expression of S100A4 in endometrial carcinoma

Modulation of mts1 expression in mouse and human normal and tumor cells

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