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| 1 | New insights into estrogenic regulation of O^6-methylguanine DNA-methyltransferase (MGMT) in human breast cancer cells: Co-degradation of ER-α and MGMT proteins by fulvestrant or O^6-benzylguanine indicates fresh avenues for therapy显示文摘Endocrine therapy using estrogen receptor-α(ER-α) antagonists for attenuating horm2one-driven cell proliferation is a major treatment modality for breast cancers.To exploit any DNA repair deficiencies associated with endocrine therapy,we investigated the functional and physical interactions of ER-α with O^6-methylguanine DNA methyltransferase(MGMT),a unique DNA repair protein that confers tumor resistance to various anticancer alkylating agents.The ER-α-positive breast cancer cell lines(MCF-7,T47D) and ER- negative cell lines(MDAMB-468,MDAMB-231),and established inhibitors of ER-α and MGMT,namely,ICI-182,780(Faslodex) and O^6-benzylguanine,respectively,were used to study MGMT- ER interactions.The MGMT gene promoter was found to harbor one full and two half estrogen-responsive elements(EREs) and two antioxidant-responsive elements(AREs).MGMT expression was upregulated by estrogen,downregulated by tamoxifen in Western blot and promoter-linked reporter assays.Similarly,both transient and stable transfections of Nrf-2(nuclear factor-erythroid 2-related factor-2)increased the levels of MGMT protein and activity 3 to 4-fold reflecting novel regulatory nodes for this drugresistance determinant.Of the different ER-α antagonists tested,the pure anti-estrogen fulvestrant was most potent in inhibiting the MGMT activity in a dose,time and ER-α dependent manner,similar to O^6-benzylguanine.Interestingly,fulvestrant exposure led to a degradation of both ER-α and MGMT proteins and O^6-benzylguanine also induced a specific loss of ER-α and MGMT proteins in MCF-7 and T47 D breast cancer cells with similar kinetics.Immunoprecipitation revealed a specific association of ER-α and MGMT proteins in breast cancer cells.Furthermore,silencing of MGMT gene expression triggered a decrease in the levels of both MGMT and ER-α proteins.The involvement of proteasome in the drug-induced degradation of both proteins was also demonstrated.Fulvestrant enhanced the cytotoxicity of MGMT-targeted alkylating agents,namely,temozolomide and BCNU by 3 to 4-fold in ER-α positive cells,but not in ER-negative cells.We conclude that MGMT and ER-α proteins exist as a complex and are co-targeted for ubiquitin-conjugation and subsequent proteasomal degradation.The findings offer a clear rationale for combining alkylating agents with endocrine therapy. | Ameya Paranjpe Nathan I. Bailes Santhi Konduri George C. Bobustuc Francis Ali-Osman Mohd. A. Yusuf Surendra R. Punganuru Hanumantha Rao Madal Debasish Basak AGM Mostofa Kalkunte S. Srivenugopa | 2016 | The Journal of Biomedical Research2016，30，5： | 5 |
| 2 | Analysis of crankshaft bear- ing using a mass conserving algorithm 显示文摘 | Paranjpe R S Goenka P K | 1990 | Tribology Transactions1990，33，3： | 1 |
| 3 | Effects of mineral tri-oxide aggregate on human dental pulp cells after pulp-cap-ping procedures显示文摘 | Paranjpe A Zhang H Johnson JD | 2010 | Endod2010，36，6： | 1 |
| 4 | Tumor-targeted bioconjugate based delivery of camptothecin:design,synthesis and in vitro evaluation显示文摘 | Paranjpe PV Chen Y Kholodovych V | 2004 | J Control Release2004，100，2： | 1 |
| 5 | Relationship of plant density to fruit yield of ' Sweet Charlie' strawberry grown in a pine bark soilless medium in a high-roof passively ventila- ted greenhouse 显示文摘 | ASHWIN V PARANJPE DANIEL J | 2008 | Scientia Horticulturae2008，115，2： | 1 |
| 6 | Phylogenetic analysis of the envelope gene ofJapanese encephalitis virus显示文摘 | PARANJPE S BANERJEE K | 1996 | Virus Res1996，2，： | 1 |
| 7 | Efficacy of the self- adjusting file system on cleaning and shaping oval canals : a microbiolog- ical and microscopic evaluation显示文摘 | Paranjpe A de Gregorio C Gonzalez AM | 2012 | J Endod2012，38，2： | 1 |
| 8 | Relationship of plant density to fruit yield of' Sweet Charlie' strawberry grown in a pine bark soiliess medium in a high-roof passively ventilated greenhouse 显示文摘 | PARANJPE A V CANTLIFFE D J STOFFELIA P J | 2008 | Scientia horticulturae2008，115，2： | 1 |
| 9 | Analysis of Crankshaft Bearing Using a Mass Conserving Algorithm 显示文摘 | Rohit S Paranjpe Pawan K Goenka | 1990 | Tribology Transaction1990，33，： | 1 |
| 10 | 显示文摘 | Paranjpe A P Mcvitte J P Self S A | 1990 | J Appl Phys1990，67，： | 1 |
| 11 | Ultralarge Scale integrated metallization and interconnects显示文摘 | Whitman C Moslehi M N Paranjpe A | | 0，，： | 1 |
| 12 | Fusobacteriurn nu- cleatum outer membrane proteins Fap2 and RadD induce cell death in human lymphocytes 显示文摘 | Kaplan CW Ma X Paranjpe A | 2010 | Infect Immun2010，78，11： | 1 |
| 13 | Enhancing the anticancer efficacy of camptothecin using biotinylated poly(ethylene glycol)conjugates in sensitive and multidrug-resistant human ovarian carcinoma cells 显示文摘 | Minko T Paranjpe PV Qiu B | 2002 | Cancer Chemother Pharmacol2002，50，2： | 1 |
| 14 | Liver Preservation With Machine Perfusion and a Newly Developed Cell‐Free Oxygen Carrier Solution Under Subnormothermic Conditions显示文摘 | P. Fontes R. Lopez A. van der Plaats Y. Vodovotz M. Minervini V. Scott K. Soltys S. Shiva S. Paranjpe D. Sadowsky D. Barclay R. Zamora D. Stolz A. Demetris G. Michalopoulos J. W. Marsh | 2015 | American Journal of Transplantation2015，，2： | 1 |
| 15 | N-acetyl cysteine protects pulp cells from resin toxins in vivo 显示文摘 | Paranjpe A Sung EC Cacalano NA | 2008 | J Dent Res2008，87，6： | 1 |
| 16 | Tumor-targeted and activat-ed bioconjugates for improved camptothecin delivery显示文摘 | Paranjpe P V Stein S Sinko P J | 2005 | Anti-cancer Drugs2005，16，7： | 1 |
| 17 | Genotypic variation in the photosynthetic competence of Sorghum bicolor seedlings subjected to polyethylene glycol-mediated drought stress显示文摘 | Bhargava S Paranjpe S | 2004 | J Plant Physlol2004，161，1： | 1 |
| 18 | Spiral CT of the lungs: optimal technique and resolution compared with conventional CT显示文摘 | PARANJPE D V BERGIN C J | 1994 | AJR1994，162，： | 1 |
| 19 | Increased lysis of stem cells but not their differentiated ceils by natural killer cells;de-differentiation or reprogramming activates NK cells显示文摘 | Tseng HC Arasteh A Paranjpe A | | 0，，07： | 1 |
| 20 | High throughput screening of methylation status of genes in prostate cancer using an oligonucleotide methylation array 显示文摘 | Yu Y P Paranjpe S Nelson J | 2005 | Carcinogenesis2005，26，： | 1 |
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