Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 19

Publication Record


Cardiology Patient Page. ABCDE Steps for Heart and Vascular Wellness Following a Prostate Cancer Diagnosis.
Guan J, Khambhati J, Jones LW, Morgans A, Allaf M, Penson DF, Moslehi J
(2015) Circulation 132: e218-20
MeSH Terms: Adenocarcinoma, Androgen Antagonists, Androgens, Antineoplastic Agents, Hormonal, Cardiovascular Diseases, Comorbidity, Diabetes Mellitus, Diet, Disease Susceptibility, Exercise, Health Promotion, Humans, Hypercholesterolemia, Hypertension, Life Style, Male, Neoplasms, Hormone-Dependent, Prostatic Neoplasms, Risk Factors, Smoking Cessation, Survivors
Added February 4, 2016
0 Communities
2 Members
0 Resources
21 MeSH Terms
Kinome-wide functional screen identifies role of PLK1 in hormone-independent, ER-positive breast cancer.
Bhola NE, Jansen VM, Bafna S, Giltnane JM, Balko JM, Estrada MV, Meszoely I, Mayer I, Abramson V, Ye F, Sanders M, Dugger TC, Allen EV, Arteaga CL
(2015) Cancer Res 75: 405-14
MeSH Terms: Animals, Antineoplastic Combined Chemotherapy Protocols, Breast Neoplasms, Cell Cycle Proteins, Drug Synergism, Estradiol, Estrogen Receptor alpha, Female, Fulvestrant, Humans, MCF-7 Cells, Mice, Mice, Nude, Neoplasms, Hormone-Dependent, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Pteridines, RNA, Small Interfering, Random Allocation, Transcription Factors, Transcription, Genetic, Xenograft Model Antitumor Assays, bcl-X Protein
Show Abstract · Added January 20, 2015
Estrogen receptor (ER) α-positive breast cancers initially respond to antiestrogens but eventually become estrogen independent and recur. ER(+) breast cancer cells resistant to long-term estrogen deprivation (LTED) exhibit hormone-independent ER transcriptional activity and growth. A kinome-wide siRNA screen using a library targeting 720 kinases identified Polo-like kinase 1 (PLK1) as one of the top genes whose downregulation resulted in inhibition of estrogen-independent ER transcriptional activity and growth of LTED cells. High PLK1 mRNA and protein correlated with a high Ki-67 score in primary ER(+) breast cancers after treatment with the aromatase inhibitor letrozole. RNAi-mediated knockdown of PLK1 inhibited ER expression, estrogen-independent growth, and ER transcription in MCF7 and HCC1428 LTED cells. Pharmacologic inhibition of PLK1 with volasertib, a small-molecule ATP-competitive PLK1 inhibitor, decreased LTED cell growth, ER transcriptional activity, and ER expression. Volasertib in combination with the ER antagonist, fulvestrant, decreased MCF7 xenograft growth in ovariectomized mice more potently than each drug alone. JUNB, a component of the AP-1 complex, was expressed 16-fold higher in MCF7/LTED compared with parental MCF7 cells. Furthermore, JUNB and BCL2L1 (which encodes antiapoptotic BCL-xL) mRNA levels were markedly reduced upon volasertib treatment in MCF7/LTED cells, while they were increased in parental MCF7 cells. Finally, JUNB knockdown decreased ER expression and transcriptional activity in MCF7/LTED cells, suggesting that PLK1 drives ER expression and estrogen-independent growth via JUNB. These data support a critical role of PLK1 in acquired hormone-independent growth of ER(+) human breast cancer and is therefore a promising target in tumors that have escaped estrogen deprivation therapy.
©2014 American Association for Cancer Research.
0 Communities
2 Members
0 Resources
23 MeSH Terms
Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer.
Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, Ferrer-Lozano J, Perez-Fidalgo JA, Cristofanilli M, Gómez H, Arteaga CL, Giltnane J, Balko JM, Cronin MT, Jarosz M, Sun J, Hawryluk M, Lipson D, Otto G, Ross JS, Dvir A, Soussan-Gutman L, Wolf I, Rubinek T, Gilmore L, Schnitt S, Come SE, Pusztai L, Stephens P, Brown M, Miller VA
(2014) Clin Cancer Res 20: 1757-1767
MeSH Terms: Breast Neoplasms, Estrogen Receptor alpha, Female, High-Throughput Nucleotide Sequencing, Humans, MCF-7 Cells, Mutation, Neoplasm Staging, Neoplasms, Hormone-Dependent
Show Abstract · Added March 7, 2014
PURPOSE - We undertook this study to determine the prevalence of estrogen receptor (ER) α (ESR1) mutations throughout the natural history of hormone-dependent breast cancer and to delineate the functional roles of the most commonly detected alterations.
EXPERIMENTAL DESIGN - We studied a total of 249 tumor specimens from 208 patients. The specimens include 134 ER-positive (ER(+)/HER2(-)) and, as controls, 115 ER-negative (ER(-)) tumors. The ER(+) samples consist of 58 primary breast cancers and 76 metastatic samples. All tumors were sequenced to high unique coverage using next-generation sequencing targeting the coding sequence of the estrogen receptor and an additional 182 cancer-related genes.
RESULTS - Recurring somatic mutations in codons 537 and 538 within the ligand-binding domain of ER were detected in ER(+) metastatic disease. Overall, the frequency of these mutations was 12% [9/76; 95% confidence interval (CI), 6%-21%] in metastatic tumors and in a subgroup of patients who received an average of 7 lines of treatment the frequency was 20% (5/25; 95% CI, 7%-41%). These mutations were not detected in primary or treatment-naïve ER(+) cancer or in any stage of ER(-) disease. Functional studies in cell line models demonstrate that these mutations render estrogen receptor constitutive activity and confer partial resistance to currently available endocrine treatments.
CONCLUSIONS - In this study, we show evidence for the temporal selection of functional ESR1 mutations as potential drivers of endocrine resistance during the progression of ER(+) breast cancer.
©2014 AACR.
0 Communities
3 Members
0 Resources
9 MeSH Terms
A kinome-wide screen identifies the insulin/IGF-I receptor pathway as a mechanism of escape from hormone dependence in breast cancer.
Fox EM, Miller TW, Balko JM, Kuba MG, Sánchez V, Smith RA, Liu S, González-Angulo AM, Mills GB, Ye F, Shyr Y, Manning HC, Buck E, Arteaga CL
(2011) Cancer Res 71: 6773-84
MeSH Terms: Adenocarcinoma, Animals, Antineoplastic Agents, Hormonal, Breast Neoplasms, Cell Line, Tumor, Disease-Free Survival, Estradiol, Estrogen Receptor Modulators, Estrogens, Female, Fulvestrant, Gene Expression Regulation, Neoplastic, Humans, Imidazoles, Insulin, Insulin-Like Growth Factor I, Mice, Mice, Nude, Neoplasm Proteins, Neoplasms, Hormone-Dependent, Protein-Tyrosine Kinases, Pyrazines, RNA Interference, Random Allocation, Receptor, IGF Type 1, Receptor, Insulin, Receptors, Estrogen, Signal Transduction, Tamoxifen, Xenograft Model Antitumor Assays
Show Abstract · Added February 13, 2014
Estrogen receptor α (ER)-positive breast cancers adapt to hormone deprivation and become resistant to antiestrogens. In this study, we sought to identify kinases essential for growth of ER(+) breast cancer cells resistant to long-term estrogen deprivation (LTED). A kinome-wide siRNA screen showed that the insulin receptor (InsR) is required for growth of MCF-7/LTED cells. Knockdown of InsR and/or insulin-like growth factor-I receptor (IGF-IR) inhibited growth of 3 of 4 LTED cell lines. Inhibition of InsR and IGF-IR with the dual tyrosine kinase inhibitor OSI-906 prevented the emergence of hormone-independent cells and tumors in vivo, inhibited parental and LTED cell growth and PI3K/AKT signaling, and suppressed growth of established MCF-7 xenografts in ovariectomized mice, whereas treatment with the neutralizing IGF-IR monoclonal antibody MAB391 was ineffective. Combined treatment with OSI-906 and the ER downregulator fulvestrant more effectively suppressed hormone-independent tumor growth than either drug alone. Finally, an insulin/IGF-I gene expression signature predicted recurrence-free survival in patients with ER(+) breast cancer treated with the antiestrogen tamoxifen. We conclude that therapeutic targeting of both InsR and IGF-IR should be more effective than targeting IGF-IR alone in abrogating resistance to endocrine therapy in breast cancer.
©2011 AACR.
0 Communities
4 Members
0 Resources
30 MeSH Terms
A gene expression signature from human breast cancer cells with acquired hormone independence identifies MYC as a mediator of antiestrogen resistance.
Miller TW, Balko JM, Ghazoui Z, Dunbier A, Anderson H, Dowsett M, González-Angulo AM, Mills GB, Miller WR, Wu H, Shyr Y, Arteaga CL
(2011) Clin Cancer Res 17: 2024-34
MeSH Terms: Anastrozole, Antineoplastic Agents, Hormonal, Biomarkers, Tumor, Breast Neoplasms, Cell Line, Tumor, Cell Proliferation, Chemotherapy, Adjuvant, Disease-Free Survival, Drug Resistance, Neoplasm, Estrogen Receptor Modulators, Female, Gene Expression Profiling, Genetic Association Studies, Humans, Kaplan-Meier Estimate, Ki-67 Antigen, Letrozole, Neoadjuvant Therapy, Neoplasm Recurrence, Local, Neoplasms, Hormone-Dependent, Nitriles, Oligonucleotide Array Sequence Analysis, Proportional Hazards Models, Proto-Oncogene Proteins c-myc, RNA Interference, Tamoxifen, Treatment Outcome, Triazoles
Show Abstract · Added February 13, 2014
PURPOSE - Although most patients with estrogen receptor α (ER)-positive breast cancer initially respond to endocrine therapy, many ultimately develop resistance to antiestrogens. However, mechanisms of antiestrogen resistance and biomarkers predictive of such resistance are underdeveloped.
EXPERIMENTAL DESIGN - We adapted four ER(+) human breast cancer cell lines to grow in an estrogen-depleted medium. A gene signature of estrogen independence was developed by comparing expression profiles of long-term estrogen-deprived (LTED) cells to their parental counterparts. We evaluated the ability of the LTED signature to predict tumor response to neoadjuvant therapy with an aromatase inhibitor and disease outcome following adjuvant tamoxifen. We utilized Gene Set Analysis (GSA) of LTED cell gene expression profiles and a loss-of-function approach to identify pathways causally associated with resistance to endocrine therapy.
RESULTS - The LTED gene expression signature was predictive of high tumor cell proliferation following neoadjuvant therapy with anastrozole and letrozole, each in different patient cohorts. This signature was also predictive of poor recurrence-free survival in two studies of patients treated with adjuvant tamoxifen. Bioinformatic interrogation of expression profiles in LTED cells revealed a signature of MYC activation. The MYC activation signature and high MYC protein levels were both predictive of poor outcome following tamoxifen therapy. Finally, knockdown of MYC inhibited LTED cell growth.
CONCLUSIONS - A gene expression signature derived from ER(+) breast cancer cells with acquired hormone independence predicted tumor response to aromatase inhibitors and associated with clinical markers of resistance to tamoxifen. Activation of the MYC pathway was associated with this resistance.
1 Communities
3 Members
0 Resources
28 MeSH Terms
Cytokine receptor CXCR4 mediates estrogen-independent tumorigenesis, metastasis, and resistance to endocrine therapy in human breast cancer.
Rhodes LV, Short SP, Neel NF, Salvo VA, Zhu Y, Elliott S, Wei Y, Yu D, Sun M, Muir SE, Fonseca JP, Bratton MR, Segar C, Tilghman SL, Sobolik-Delmaire T, Horton LW, Zaja-Milatovic S, Collins-Burow BM, Wadsworth S, Beckman BS, Wood CE, Fuqua SA, Nephew KP, Dent P, Worthylake RA, Curiel TJ, Hung MC, Richmond A, Burow ME
(2011) Cancer Res 71: 603-13
MeSH Terms: Animals, Antineoplastic Agents, Hormonal, Breast Neoplasms, Cell Line, Tumor, Drug Resistance, Neoplasm, Estradiol, Estrogen Antagonists, Female, Fulvestrant, Humans, MAP Kinase Signaling System, Mice, Mice, SCID, Neoplasm Metastasis, Neoplasms, Hormone-Dependent, Receptors, CXCR4, Receptors, Estrogen
Show Abstract · Added June 14, 2013
Estrogen independence and progression to a metastatic phenotype are hallmarks of therapeutic resistance and mortality in breast cancer patients. Metastasis has been associated with chemokine signaling through the SDF-1-CXCR4 axis. Thus, the development of estrogen independence and endocrine therapy resistance in breast cancer patients may be driven by SDF-1-CXCR4 signaling. Here we report that CXCR4 overexpression is indeed correlated with worse prognosis and decreased patient survival irrespective of the status of the estrogen receptor (ER). Constitutive activation of CXCR4 in poorly metastatic MCF-7 cells led to enhanced tumor growth and metastases that could be reversed by CXCR4 inhibition. CXCR4 overexpression in MCF-7 cells promoted estrogen independence in vivo, whereas exogenous SDF-1 treatment negated the inhibitory effects of treatment with the anti-estrogen ICI 182,780 on CXCR4-mediated tumor growth. The effects of CXCR4 overexpression were correlated with SDF-1-mediated activation of downstream signaling via ERK1/2 and p38 MAPK (mitogen activated protein kinase) and with an enhancement of ER-mediated gene expression. Together, these results show that enhanced CXCR4 signaling is sufficient to drive ER-positive breast cancers to a metastatic and endocrine therapy-resistant phenotype via increased MAPK signaling. Our findings highlight CXCR4 signaling as a rational therapeutic target for the treatment of ER-positive, estrogen-independent breast carcinomas needing improved clinical management.
© 2010 AACR.
2 Communities
4 Members
0 Resources
17 MeSH Terms
The PPARγ ligand ciglitazone regulates androgen receptor activation differently in androgen-dependent versus androgen-independent human prostate cancer cells.
Moss PE, Lyles BE, Stewart LV
(2010) Exp Cell Res 316: 3478-88
MeSH Terms: Androgen-Binding Protein, Cell Line, Tumor, Cell Proliferation, Cyclin D1, Dihydrotestosterone, Gene Expression, Genes, Reporter, Humans, Hypoglycemic Agents, Male, Mutation, Neoplasms, Hormone-Dependent, PPAR gamma, Prostate-Specific Antigen, Prostatic Neoplasms, RNA, Small Interfering, Receptors, Androgen, Rosiglitazone, Thiazolidinediones, Transfection
Show Abstract · Added March 27, 2014
The androgen receptor (AR) regulates growth and progression of androgen-dependent as well as androgen-independent prostate cancer cells. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists have been reported to reduce AR activation in androgen-dependent LNCaP prostate cancer cells. To determine whether PPARγ ligands are equally effective at inhibiting AR activity in androgen-independent prostate cancer, we examined the effect of the PPARγ ligands ciglitazone and rosiglitazone on C4-2 cells, an androgen- independent derivative of the LNCaP cell line. Luciferase-based reporter assays and Western blot analysis demonstrated that PPARγ ligand reduced dihydrotestosterone (DHT)-induced increases in AR activity in LNCaP cells. However, in C4-2 cells, these compounds increased DHT-induced AR driven luciferase activity. In addition, ciglitazone did not significantly alter DHT-mediated increases in prostate specific antigen (PSA) protein or mRNA levels within C4-2 cells. siRNA-based experiments demonstrated that the ciglitazone-induced regulation of AR activity observed in C4-2 cells was dependent on the presence of PPARγ. Furthermore, overexpression of the AR corepressor cyclin D1 inhibited the ability of ciglitazone to induce AR luciferase activity in C4-2 cells. Thus, our data suggest that both PPARγ and cyclin D1 levels influence the ability of ciglitazone to differentially regulate AR signaling in androgen-independent C4-2 prostate cancer cells.
Copyright © 2010 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Breast cancer. Clinical practice guidelines in oncology.
Carlson RW, Allred DC, Anderson BO, Burstein HJ, Carter WB, Edge SB, Erban JK, Farrar WB, Goldstein LJ, Gradishar WJ, Hayes DF, Hudis CA, Jahanzeb M, Kiel K, Ljung BM, Marcom PK, Mayer IA, McCormick B, Nabell LM, Pierce LJ, Reed EC, Smith ML, Somlo G, Theriault RL, Topham NS, Ward JH, Winer EP, Wolff AC, NCCN Breast Cancer Clinical Practice Guidelines Panel
(2009) J Natl Compr Canc Netw 7: 122-92
MeSH Terms: Algorithms, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Aromatase Inhibitors, Breast, Breast Neoplasms, Combined Modality Therapy, Female, Humans, Lymphatic Metastasis, Mastectomy, Neoadjuvant Therapy, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Neoplasm Staging, Neoplasms, Hormone-Dependent, Postmenopause, Premenopause, Randomized Controlled Trials as Topic, Receptor, ErbB-2, Selective Estrogen Receptor Modulators, Sentinel Lymph Node Biopsy, Tamoxifen, Trastuzumab
Added March 5, 2014
0 Communities
1 Members
0 Resources
24 MeSH Terms
The nuclear factor-kappaB pathway controls the progression of prostate cancer to androgen-independent growth.
Jin RJ, Lho Y, Connelly L, Wang Y, Yu X, Saint Jean L, Case TC, Ellwood-Yen K, Sawyers CL, Bhowmick NA, Blackwell TS, Yull FE, Matusik RJ
(2008) Cancer Res 68: 6762-9
MeSH Terms: Androgens, Animals, Apoptosis, Blotting, Western, Carcinoma, Neuroendocrine, Castration, Cell Nucleus, Disease Progression, Gene Expression Regulation, Neoplastic, Humans, I-kappa B Kinase, Male, Mice, Mice, Knockout, NF-kappa B, Neoplasms, Hormone-Dependent, Prostatic Neoplasms, RNA, Messenger, Receptors, Androgen, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Transcription, Genetic, Tumor Cells, Cultured
Show Abstract · Added February 26, 2013
Typically, the initial response of a prostate cancer patient to androgen ablation therapy is regression of the disease. However, the tumor will progress to an "androgen-independent" stage that results in renewed growth and spread of the cancer. Both nuclear factor-kappaB (NF-kappaB) expression and neuroendocrine differentiation predict poor prognosis, but their precise contribution to prostate cancer progression is unknown. This report shows that secretory proteins from neuroendocrine cells will activate the NF-kappaB pathway in LNCaP cells, resulting in increased levels of active androgen receptor (AR). By blocking NF-kappaB signaling in vitro, AR activation is inhibited. In addition, the continuous activation of NF-kappaB signaling in vivo by the absence of the IkappaBalpha inhibitor prevents regression of the prostate after castration by sustaining high levels of nuclear AR and maintaining differentiated function and continued proliferation of the epithelium. Furthermore, the NF-kappaB pathway was activated in the ARR(2)PB-myc-PAI (Hi-myc) mouse prostate by cross-breeding into a IkappaBalpha(+/-) haploid insufficient line. After castration, the mouse prostate cancer continued to proliferate. These results indicate that activation of NF-kappaB is sufficient to maintain androgen-independent growth of prostate and prostate cancer by regulating AR action. Thus, the NF-kappaB pathway may be a potential target for therapy against androgen-independent prostate cancer.
3 Communities
4 Members
0 Resources
23 MeSH Terms
Proteomics of cancer of hormone-dependent tissues.
Tyson DR, Ornstein DK
(2008) Adv Exp Med Biol 630: 133-47
MeSH Terms: Biomarkers, Tumor, Body Fluids, Humans, Neoplasm Proteins, Neoplasms, Neoplasms, Hormone-Dependent, Proteomics, Tumor Cells, Cultured
Show Abstract · Added February 27, 2013
Serum and tissue biomarkers have begun to play an increasingly important role in the detection and management of many cancers of hormone-sensitive tissues. Specifically, the introduction of serum PSA measurements into clinical practice has dramatically altered detection and treatment of prostate cancer and serum tumor markers play a critical role in the management of testicular cancer. Serum biomarkers are used for ovarian and pancreatic cancers, but their usefulness is limited by poor specificity. Tissue biomarkers are used to help guide breast cancer treatment but are not widely used in other cancers. Even the "best" biomarkers such as PSA have substantial limitations. The discovery of new biomarkers for both early detection and prognosis of cancer is critical to the hope of better clinical outcomes. Recently there has been an expanding understanding of the underlying molecular etiology of cancer and molecular targeted therapies for some particularly aggressive cancers such as renal cell carcinoma have been developed. Better understanding of the molecular etiology of cancer and identification of additional therapeutic targets remain important research goals. Currently, there are very few patient-tailored therapies and there is a great need to better understand the molecular alterations associated with cancer and to use this information to design need cancer therapies and prevention strategies. Advances in proteomic technologies have created tremendous opportunities for biomarker discovery and biological studies of cancer. The potential that proteomics will impact clinical practice is currently greater than ever, but there main several obstacles in making this a reality. A major hurdle to overcome continues to be the proper acquisition of patient tissues and body fluids for investigation and clinical diagnostics. Each cancer has specific issues in this regard and it is incumbent upon investigators and collaborating clinicians to understand the various nuances of tissue and biofluid procurement. This chapter not only reviews the clinical need and potential impact of proteomic studies of hormone-sensitive cancers, but details specific technologies and discusses the issues surrounding tissue/biofluid procurement.
0 Communities
1 Members
0 Resources
8 MeSH Terms