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  • 1
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Cancer Research and Clinical Oncology Vol. 148, No. 10 ( 2022-10), p. 2881-2891
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 148, No. 10 ( 2022-10), p. 2881-2891
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2018
    In:  Cancer Research Vol. 78, No. 13_Supplement ( 2018-07-01), p. 1128-1128
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 1128-1128
    Abstract: Nuclear respiratory factor 1 (NRF1) and inhibitor of differentiation protein 3 (ID3) are transcription regulating proteins. Recently we have uncovered a novel oncogenic function of NRF1 in breast cancer development and progression. In this study, we tested the postulate that exposure to PCB153 contributes in ID3 over-expressing endothelial stem cells (EndSCs) chaperoning and guiding of mesenchymal NRF1 breast cancer stem cells (BCSCs) across the blood-brain barrier. BCSCs/EndSCs were subjected to functional gain/loss of ID3 and/or NRF1 to test if PCB153 [1ng/ml] exposure produces NRF/ID3 signals regulating lineage specific BCSCs organ entry. First, we tested whether NRF1 promotes transmigration of breast cancer using a 3D blood-brain barrier (BBB) model consisting of breast tumor initiating cells (BTICs) or MDAMB231 cells, brain endothelial cell layer, and astrocytes. NRF1 overexpression increased the propensity for BTICs and mesenchymal enriched MDAMB231 BCSCs to adhere to brain endothelial cells and migrate across a human BBB model. Increased adhesion of NRF1+ BCSCs with ID3+ EndSCs was detected. ID3 EndSCs promoted the transmigration of BCSCs through the BBB. We found differential effects by endocrine disruptors, namely PCB153 and PCB77. The treatment with PCB153 showed increased growth of NRF1+ BCSCs tumor spheroids. PCB153 also induced the tumor cell adhesion to microvascular endothelium and transendothelial migration of BCSCs. The exosomal ID3 released from endothelial cells helped the mesenchymal NRF1+ BCSCs to cross through blood brain barriers. Xenograft experiments showed that ID3+ brain EndSCs not only supported the growth of estrogen treated NRF1+ BCSC tumorospheroids, but guided them to the brain in zebrafish. These findings show for the first time a key role for ID3 and NRF1 by which specific circulatory EndSCs accompany a particular sub-type of BCSCs to distant metastatic sites where they most likely facilitate the seeding, survival, and proliferation of BCSCs. This knowledge is important for pre-clinical testing of NRF1/ID3 modifying agents that prevent the spread of breast cancer to the brain. This work was, in part, supported by a VA MERIT Review (VA BX001463) grant to DR. Citation Format: Jayanta K. Das, Mayur Doke, Alok Deoraj, Quentin Felty, Deodutta Roy. Exosomal ID3 is pro-metastatic through guiding NRF1-induced breast cancer stem cells across the blood-brain-barrier [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1128.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 3433-3433
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 3433-3433
    Abstract: The main objective of this study was to examine the cross-sectional relationship between exposure to PCBs or their congeners and breast cancer among US women. There is limited information on the association of specific PCB congener or their combination levels in blood serum with increased breast cancer risk. PCBs are weak estrogens which has been shown to act as endocrine disrupters by increasing or blocking estrogen like activities in animals and humans. We analyzed National Health and Nutrition Examination Survey (NHANES) data from 1999-2004 in the lipid adjusted blood samples of female participants ( & gt;20 years of age). Exposure assessment was based on lipid adjusted serum levels of 6 individual PCB congeners (PCB 074, 099, 118, 138, 153, and 180), the sum of dioxin-like PCBs (074 and 118), and the sum of non-dioxin-like PCBs (099 + 138 + 153+187) in conjunction with data obtained from the medical and reproductive health questionnaires. We calculated geometric means to compare PCB concentrations in women's blood samples who also self-reported a breast cancer diagnosis and women who were never diagnosed with cancer. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CI) for the association between PCB, their congener or their combinations and breast cancer. We evaluated age, race/ethnicity, age at menarche, body mass index (BMI; kg/m2), and lactation as potential confounders. Our results show a weighted geometric mean levels of 6 PCB congeners to be significantly higher in blood serum among women with breast cancer when compared to the rest of the study population. After adjusting for age, race, BMI, lactation, and age at menarche we found significant association of PCB 138 with breast cancer [odds ratios of 2.88; 95% confidence interval (CI): 1.14-7.30; 2.93, 95% CI: 1.04-8.26; and 3.43, 95% CI: 1.12-10.4] in women with higher body burdens of individual PCB congeners ( & gt; 50th percentile, 50th-75th percentile, and ≥75th percentile), respectively. After adjusting for age and race, it was also found that the sum of non-dioxin-like PCBs (074 and 118) in blood serum is significantly associated with breast cancer [OR of 1.14; 95% CI: 1.00-1.29]. In summary, our results suggest a possible link between environmental exposures to PCBs and increased risk of breast cancer among U.S. women. Citation Format: Marisa Morgan, Alok Deoraj, Deodutta Roy. Association between serum concentrations of polychlorinated biphenyls (PCBs) and increased risk of breast cancer among US women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3433.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    In: Journal of Cancer Research and Clinical Oncology, Springer Science and Business Media LLC, Vol. 148, No. 7 ( 2022-07), p. 1641-1682
    Type of Medium: Online Resource
    ISSN: 0171-5216 , 1432-1335
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1459285-X
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  • 5
    Online Resource
    Online Resource
    Microbiology Society ; 2020
    In:  Journal of Medical Microbiology Vol. 69, No. 1 ( 2020-01-01), p. 14-24
    In: Journal of Medical Microbiology, Microbiology Society, Vol. 69, No. 1 ( 2020-01-01), p. 14-24
    Type of Medium: Online Resource
    ISSN: 0022-2615 , 1473-5644
    RVK:
    Language: English
    Publisher: Microbiology Society
    Publication Date: 2020
    detail.hit.zdb_id: 2083944-3
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2015
    In:  Cancer Research Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4559-4559
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4559-4559
    Abstract: Although several nuclear regulatory proteins may be targeted by estrogen, our efforts have focused on the redox nuclear respiratory factor-1 (NRF-1), because our recent study showed that NRF-1 gene expression significantly increases with the progression of breast tumor grades. NRF-1 overexpression supported in vitro tumor formation. To determine if NRF-1 is required for 17 beta estradiol (E2)-induced neoplastic phenotype, we have generated NRF-1 mutants by site directed mutagenesis. We have generated stable clones that express NRF-1 mutant. The in vitro tumor formation was detected by anchorage independent growth and 3D spheroid assays. NRF-1 overexpression enhanced in vitro tumor spheroid formation, cell migration and cell invasion. Our flow cytometry analysis showed that overexpression of wild-type NRF-1 increased the percent of transformed MCF-10A cells in S phase compared to vector alone. Dominant negative NRF-1 protein showed reduction in the tumor formation. In addition, shRNA targeting NRF-1 resulted in the inhibition of anchorage independent growth of MCF-10A cells in both vehicle control and E2-treated cells. Since NRF-1 is a substrate of the kinase AKT, we determined whether NRF-1 phosphorylation was increased in MCF-10A cells after treatment with a carcinogenic regimen of E2. We observed more than a 2-fold increase in phospho-NRF-1 in E2 treated (100pg/ml for 30 min) MCF-10A cells and phosphorylation of NRF-1 was inhibited by co-treatment with either biological (CAT or MnSOD) or chemical (20μM ebselen) ROS modifiers. These results suggest that E2-induced phosphorylation of NRF-1 is influenced by ROS signaling messengers. We found that E2 treated MCF-10A cells showed increased NRF-1 binding to the promoters of Cdc2, PRC1, PCNA, Cyclin B1, and CDC25C genes. NRF-1 binding induced by E2 treatment was inhibited by the overexpression of CAT and MnSOD. NRF-1 phosphorylation site specific to kinase AKT, Thr-109, was mutated to Asp (D) or Ala (A), and the NRF-1 acetylation site specific to acetyl-transferase PCAF, Lys- 89, was mutated to Gln (glutamine)-Q or Ala (A). We examine the effect of one of the NRF-1 mutants on E2-induced in vitro tumor formation. We observed that the expression of NRF-1 (T109A) phosphodeficient mutant (NRF-1PMT) significantly inhibited E2-induced cell transformation, whereas empty vector did not influence E2-induced colony formation. Together these findings support the idea that NRF-1 may play an important role in E2-induced malignant transformation of breast epithelial cells. Thus, our data is consistent with the hypothesis that in addition to the estrogen receptor activity, NRF-1 activation contributes to the susceptibility to develop malignant phenotype in response to exposure to estrogen. This work was in part supported by a VA MERIT Review (VA BX001463) grant to DR Citation Format: Lazaro Mesa, Jayanta Das, Alok Deoraj, Victor Okoh, Deodutta Roy. Phosphodeficient NRF1 mutant suppresses the susceptibility of the breast epithelial cells to develop tumors when exposed to estrogen - a major breast cancer risk factor. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4559. doi:10.1158/1538-7445.AM2015-4559
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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