An EGF receptor inhibitor induces RAR-β expression in breast and ovarian cancer cells

Grunt, Thomas W.; Puckmair, Klaudia; Tomek, Katharina; Kainz, Birgit; Gaiger, Alexander

doi:10.1016/j.bbrc.2005.02.104

Cited by 20 publications

(29 citation statements)

References 16 publications

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“…Another recent report from Austria determined the utility of RASSF1A hypermethylation in circulating tumor specific DNA as a marker for monitoring efficacy of adjuvant therapy in 148 breast cancer patients. 46 RASSF1A hypermethylation was observed in 19.6% of pre therapeutic sera and in 22.3% of 1-year after primary surgery (and during adjuvant tamoxifen therapy). Interestingly, RASSF1A methylation 1 year after primary surgery was an independent predictor of poor outcome.…”

Section: Discussionmentioning

confidence: 99%

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Detection of RASSF1A and RAR? Hypermethylation in Serum DNA from Breast Cancer Patients

Shukla

Mirza²,

Sharma³

et al. 2006

Epigenetics

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ABBREVIATIONS RASSF1ARAS association domain family protein 1A RARβ retionic acid receptor β MSP methylation specific PCR ERα estrogen receptor α PRB progesterone receptor B ACKNOWLEDGEMENTSWe are grateful to Department of Biotechnology, India, for providing the financial support to conduct this study. S.M. is grateful to University Grant Commission for award of Junior Research Fellowship. The authors thank Dr. Cecile Rochette Egly for the kind gift of RARβ monoclonal antibody. Research PaperDetection of RASSF1A and RARβ Hypermethylation in Serum DNA from Breast Cancer Patients ABSTRACTBreast cancer is fast emerging as the leading cancer amongst females, especially in young females in metropolitan cities in India. The epigenetic alterations involved in the onset and progression of breast cancer may serve as biomarkers for early detection and prognosis of the disease. Furthermore, using body fluids such as serum offers a noninvasive method to procure multiple samples for such analyses. In this study, we examined methylation status of two normally unmethylated but biologically significant cancer genes, RAS association domain family protein 1A (RASSF1A) and retionic acid receptor β (RARβ) by methylation specific PCR (MSP) in invasive ductal carcinomas of the breast and paired serum DNA. RASSF1A was found to be methylated in 17 of 20 (85%) breast tumors; while sera from 15 of 20 (75%) of the patients showed concordant methylated RASSF1A, with a sensitivity of 88%. RARβ was methylated in 2/20 (10%) breast tumors. A gene unmethylated in the tumor DNA was always found to be unmethylated in the matched serum DNA for both RASSF1A and RARβ genes; hence specificity was 100%. Immunohistochemical analysis of RARβ protein in 15 breast carcinoma patients harboring unmethylated RARβ in tumors and serum DNA showed the expression of RARβ protein in tumors and paired normal breast tissues, confirming the MSP findings, suggesting that RARβ promoter is functional in these cases. This study underscores the potential utility of DNA methylation based screening of serum, a readily accessible body fluid, as a surrogate marker for early detection of breast cancer.

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Section: Discussionmentioning

confidence: 99%

“…Methylation of these genes, which are normally unmethylated in breast tissue, has been shown to correlate with poor breast cancer prognosis, distant metastases and patient's response to chemotherapy. 15,18,[42][43][44][45][46][47][48] …”

Section: Introductionmentioning

confidence: 99%

Detection of RASSF1A and RAR? Hypermethylation in Serum DNA from Breast Cancer Patients

Shukla

Mirza²,

Sharma³

et al. 2006

Epigenetics

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“…The observations that RAR-β 2 was upregulated in patients after treatment with 13-cis RA and that increased expression of RAR-β 2 correlated with clinical response [39] suggest that RAR-β 2 has an important role in suppressing carcinogenesis. After these findings were published, the methylation status of the RAR-β 2 gene promoter was used as a biomarker for the early detection of malignancy or as an intermediate end-point marker to monitor the efficacy of chemoprevention agents in clinical trials [50][51][52][53][54][55][56][57][58][59][60].…”

Section: Loss Of Rar-β 2 Expression As a Biomarker In Solid Tumorsmentioning

confidence: 99%

Tumor-suppressive activity of retinoic acid receptor-β in cancer

2007

Cancer Letters

119

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Retinoids, a group of structural and functional analogs of vitamin A, are known to regulate a large number of essential biological processes and to suppress carcinogenesis. The effects of retinoids are mainly mediated by nuclear retinoid receptors, which include retinoic acid receptors (RARs) and retinoid X receptors (RXRs). Each receptor has three subtypes (α, β, and γ) and each subtype has different isoforms. Retinoic acid receptor-β (RAR-β) has four isoforms that have different affinities to retinoids and different biological functions. Loss of expression of RAR-β 2 during cancer development is associated with tumorigenesis and retinoid resistance; induction of its expression, on the other hand, can suppress carcinogenesis. Expression of another isoform, RAR-β 4 , is increased in various types of cancer. RAR-β 4 transgenic mice develop hyperplasia and neoplasia in various tissues, and induction of RAR-β 4 expression increases the growth of tumor cells that do not express RAR-β 2 . Future studies will focus on molecular pathways involving RAR-β 2 and the role of RAR-β 4 in cancer development.

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“…In addition, a coordinate inactivation of a group of 3p genes by genetic or epigenetic mechanism for example under-expressed putative tumor suppressor genes, i.e. retinoic acid receptor β (RAR β) may be an important factor for the pathogenesis of ovarian cancer [11]. It has also been demonstrated that β-carotene can reach target tissues in an unchanged form and undergo metabolic transformation into retinoids directly in the ovary [15].…”

Section: Discussionmentioning

confidence: 99%

“…Since its active metabolites, mainly retinoic acid, by binding to specific nuclear receptors (RAR and RXR) activate transcription processes, retinoids seem to play chemopreventive and chemotherapeutic roles in ovarian carcinoma [11].…”

Section: Introductionmentioning

confidence: 99%

Vitamin A family compounds, estradiol, and docetaxel in proliferation, apoptosis and immunocytochemical profile of human ovary endometrioid cancer cell line CRL-11731.

Czeczuga-Semeniuk

Bielawski²,

Lemancewicz³

et al. 2010

Folia Histochem Cytobiol.

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Endometrioid carcinoma represents approximately 10% of cases of the malignant ovarian epithelial tumors. According to literature, the vitamin A (carotenoids and retinoids) plays an essential role in cell proliferation, differentiation and apoptosis in both normal and neoplastic ovarian tissues. Apart from that, the retinoids alter a cytotoxic effect of chemiotherapeutics, i.e. docetaxel, on ovarian cancer cell lines. Retinoids act on cancer cells throughout different mechanism than taxanes, so they may be the potential candidates for the new treatment strategies of ovarian cancer.The aim of the study was to determine the effects of vitamin A family compounds (retinol, β-carotene, lycopene, all-trans -, 9-cis -and 13-cis retinoic acid) on the growth and proliferation of CRL-11731 endometrioid ovary cancer cell line and on docetaxel and estradiol activity in this culture. The assay was based on [ 3 H] thymidine incorporation and the proliferative activity of PCNA-and Ki 67-positive cells. The apoptotic index and expression of the Bcl-2 and p53 antigens in CRL-11731 cells were also studied. Among vitamin A family compounds retinol and carotenoids, but not retinoids, inhibited the growth of cancer cells in dose dependent manner. Only the concentration of 100 μM of docetaxel inhibited incorporation [ 3 H] thymidine into CRL-11731 cancer cells. Retinol (33.4%±8.5), carotenoids (β-carotene 20 μM 4.7%±2.9, 50 μM 2.2%±0.9; lycopene 10 μM 7.6%±0.8, 20 μM 5.2%±2.5, 50 μM 2.9%±1.2), and 13-cis retinoic acid (19.7%±2.2) combined with docetaxel (100 μM) significantly decreased the percentage of proliferating cells (p<0.0001). The antiproliferative action of lycopene alone and in combination with docetaxel was also confirmed in immunohistochemical examination (decreased the percentage of PCNA and Ki67 positive cells). Also retinol (10 μM) and lycopene (20 and 50 μM) combined with estradiol (0.01 μM) statistically decreased the percentage of proliferating cells compared to the control (p<0.0001) and estradiol (p<0.01, p<0.0001) group (63.5%±14.8, 61.0%±20.6, 15.0%±5.5 respectively). In our experiments, the compounds tested induced an apoptotic effect. Docetaxel and estradiol increased the percentage of apoptotic cells (71% apoptotic cells after administration of 10 μM all-trans retinoic acid combined with 0.01 μM estradiol, p<0.0001). β-carotene, lycopene and all-trans retinoic acid alone and in combination with docetaxel were found to influence the expression of bcl-2 and p53 antigen in the cells examined.The results of our study justified an important role of vitamin A in the pathophysiology of the ovarian endometrioid cancer.

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An EGF receptor inhibitor induces RAR-β expression in breast and ovarian cancer cells

Cited by 20 publications

References 16 publications

Detection of RASSF1A and RAR? Hypermethylation in Serum DNA from Breast Cancer Patients

Detection of RASSF1A and RAR? Hypermethylation in Serum DNA from Breast Cancer Patients

Tumor-suppressive activity of retinoic acid receptor-β in cancer

Vitamin A family compounds, estradiol, and docetaxel in proliferation, apoptosis and immunocytochemical profile of human ovary endometrioid cancer cell line CRL-11731.

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