P11 Loss of retinoic acid receptor β expression in breast cancer and morphologically normal adjacent tissue but not in the normal breast tissue distant from the cancer

Widschwendter, Martin; Berger, Juliette; Daxenbichler, G.; Widschwendter, Andreas; Zeimet, AG; Schröcksnadel, H.; Dapunt, O

doi:10.1016/s0959-8049(97)89229-5

Cited by 82 publications

(101 citation statements)

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“…Methylation of the RARb2 gene is believed to be an early change in breast carcinogenesis. Indeed, RARb2 promoter methylation has been observed in normal, but dysplastic mammary epithelial surgical specimens of patients with breast cancer [Widschwendter et al, 1997]. We support this finding through our similar observation here that RARb2 is methylated in immortalized pretumorigenic MCF10A mammary epithelial cells.…”

Section: Discussionsupporting

confidence: 89%

Modulation of gene methylation by genistein or lycopene in breast cancer cells

King-Batoon

Leszczyńska

Klein

2008

Environ and Mol Mutagen

207

113

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Dietary agents with chemopreventive potential, including soy-derived genistein and tomato-derived lycopene, have been shown to alter gene expression in ways that can either promote or potentially inhibit the carcinogenic processes. To begin to explore the mechanisms by which these agents may be acting we have examined the DNA methylation modulating capacity of genistein or lycopene for several genes relevant to breast cancer in the breast cancer cell lines MCF-7 and MDA-MB-468, as well as in immortalized but noncancer fibrocystic MCF10A breast cells. We find using methylation specific PCR (MSP) that a low, nontoxic concentration of genistein (3.125 lM, resupplemented every 48 hr for 1 week) or a single dose of lycopene (2 lM) partially demethylates the promoter of the GSTP1 tumor suppressor gene in MDA-MB-468 cells. RT-PCR studies confirm a lack of GSTP1 expression in untreated MDA-MB-468, with restoration of GSTP1 expression after genistein or lycopene treatment. The RARb2 gene however, was not demethylated by genistein or lycopene in either of these breast cancer cell lines. But, lycopene (2 lM, once per week for 2 weeks) did induce demethylation of RARb2 and the HIN-1 genes in the noncancer MCF10A fibrocystic breast cells. These data show for the first time that the tomato carotenoid lycopene has direct DNA demethylating activity. In summary, both genistein and lycopene, at very low, dietarily relevant concentrations can potentially mitigate tumorigenic processes via promoter methylation modulation of gene expression. Environ. Mol. Mutagen. 49:36-45, 2008.

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Section: Discussionsupporting

confidence: 89%

Modulation of gene methylation by genistein or lycopene in breast cancer cells

King-Batoon

Leszczyńska

Klein

2008

Environ and Mol Mutagen

207

113

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“…Previous studies have shown that RARb and particularly its RARb2 isoform are increased in human breast epithelial cells, which after continuous (>20 passages) in vitro culturing develop senescent phenotype (41). In breast premalignant lesions and tumors, RARb2 is lost, suggesting its tumor suppressor role (42,43). Transfection of RARb2 in tumor cells lacking the receptor was associated with cell growth inhibition and induction of apoptosis (44).…”

Section: Discussionmentioning

confidence: 99%

Bexarotene Induces Cellular Senescence in MMTV-Neu Mouse Model of Mammary Carcinogenesis

Shilkaitis

Bratescu

Green

et al. 2013

Cancer Prevention Research

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Previous studies have shown that retinoids and rexinoids can prevent breast cancer in animal models and in women with increased risk of developing the disease. The cellular effects of these vitamin A analogues have been primarily associated with induction of differentiation and inhibition of proliferation. In this study, we tested the hypothesis that bexarotene (LGD1069, Targretin), a rexinoid, can not only inhibit cell proliferation but also induce cellular senescence in mammary epithelial cells, premalignant lesions, and tumors of the MMTV-Neu model of mammary carcinogenesis, which develops estrogen receptor-negative tumors. Mice with palpable mammary tumors were treated for 4 weeks with bexarotene at 80 or 40 mg/kg body weight, and senescent cells were determined by SAb-Gal assay. Bexarotene decreased in a dose-dependent manner the multiplicity of premalignant lesions and tumors, and this was associated with inhibition of cell proliferation and induction of cellular senescence and apoptosis. By double labeling of senescent cells, first by SA-b-Gal and then by antibodies against genes related to cellular senescence, we found that p21, p16, and RARb, but not p53, were upregulated by bexarotene in mammary tumors and in breast cancer cell lines, suggesting involvement of multiple signaling pathways in mediating the senescence program of rexinoids. These findings indicate that, in addition to cell proliferation and apoptosis, cellular senescence could be used as a potential biomarker of response in breast cancer prevention and therapy studies with rexinoids and possibly with other antitumor agents. Cancer Prev Res; 6(4); 299-308. Ó2013 AACR.

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“…It is considered to be a tumor suppressor gene due to its frequent loss of expression in various types of human cancer, such as esophageal, gastric, colonic and breast cancer (Widschwendter et al, 1997;Wang et al, 2003;Sun et al, 2004). Wang et al (2003) found that hypermethylation of the RARβ promoter region is an important mechanism for RARβ gene silencing in esophageal squamous cell carcinoma.…”

Section: -(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Induces Retinmentioning

confidence: 99%

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Induces Retinoic Acid Receptor β Hypermethylation through DNA Methyltransferase 1 Accumulation in Esophageal Squamous Epithelial Cells

Wang

Zhao²,

Li³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Overexpression of DNA methyltransferase 1 (DNMT1) has been detected in many cancers. Tobacco exposure is known to induce genetic and epigenetic changes in the pathogenesis of malignancy. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen present in tobacco smoke; however the detailed molecular mechanism of how NNK induces esophageal carcinogenesis is still unclear. We found that DNMT1 was overexpressed in ESCC tissues compared with paired non-cancerous tissues, the overexpression being

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P11 Loss of retinoic acid receptor β expression in breast cancer and morphologically normal adjacent tissue but not in the normal breast tissue distant from the cancer

Cited by 82 publications

References 0 publications

Modulation of gene methylation by genistein or lycopene in breast cancer cells

Modulation of gene methylation by genistein or lycopene in breast cancer cells

Bexarotene Induces Cellular Senescence in MMTV-Neu Mouse Model of Mammary Carcinogenesis

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Induces Retinoic Acid Receptor β Hypermethylation through DNA Methyltransferase 1 Accumulation in Esophageal Squamous Epithelial Cells

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