Abstract:
:One third of the patients with estrogen receptor α (ERα)-positive breast cancer who are treated with the antiestrogen tamoxifen will either not respond to initial therapy or will develop drug resistance. Endocrine response involves crosstalk between ERα and TGFβ signaling, such that tamoxifen nonresponsiveness or resistance in breast cancer might involve aberrant TGFβ signaling. In this study, we analyzed TGFβ receptor type 2 (TGFBR2) expression and correlated it with ERα status and phosphorylation in a cohort of 564 patients who had been randomized to tamoxifen or no-adjuvant treatment for invasive breast carcinoma. We also evaluated an additional four independent genetic datasets in invasive breast cancer. In all the cohorts we analyzed, we documented an association of low TGFBR2 protein and mRNA expression with tamoxifen resistance. Functional investigations confirmed that cell cycle or apoptosis responses to estrogen or tamoxifen in ERα-positive breast cancer cells were impaired by TGFBR2 silencing, as was ERα phosphorylation, tamoxifen-induced transcriptional activation of TGFβ, and upregulation of the multidrug resistance protein ABCG2. Acquisition of low TGFBR2 expression as a contributing factor to endocrine resistance was validated prospectively in a tamoxifen-resistant cell line generated by long-term drug treatment. Collectively, our results established a central contribution of TGFβ signaling in endocrine resistance in breast cancer and offered evidence that TGFBR2 can serve as an independent biomarker to predict treatment outcomes in ERα-positive forms of this disease.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Busch S,Sims AH,Stål O,Fernö M,Landberg Gdoi
10.1158/0008-5472.CAN-14-1583subject
Has Abstractpub_date
2015-04-01 00:00:00pages
1457-69issue
7eissn
0008-5472issn
1538-7445pii
75/7/1457journal_volume
75pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Methylation-mediated silencing of G0-G1 switch gene 2 (G0S2) has been detected in a variety of solid tumors, whereas G0S2 induction is associated with remissions in patients with acute promyelocytic leukemia, implying that G0S2 may possess tumor suppressor activity. In this study, we clearly demonstrate that G0S2 oppo...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2265
更新日期:2016-03-01 00:00:00
abstract::Dissemination of tumor to the leptomeninges and cerebrospinal fluid represents a common pattern of metastasis for many cancers; however, few chemotherapeutic agents are available for intrathecal (i.t.) use and treatment results are often poor. We studied the neurotoxicity and pharmacokinetics of i.t. 4-hydroperoxycycl...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-11-15 00:00:00
abstract::The olfactory marker protein (OMP) is a M(r) 19,000 polypeptide originally considered a selective marker for differentiated olfactory receptor neurons. In an attempt to induce neoplastic proliferation in the olfactory cells, we made mice transgenic for the simian virus 40 large T-antigen gene linked to the OMP gene pr...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::The binding of labeled insulin to dissociated R3230AC mammary adenocarcinoma cells from diabetic and intact rats was investigated in vitro. At 20 degrees, specific binding (total binding minus binding in the presence of 1000-fold excess or 10(-6) M unlabeled insulin) reached a plateau at 45 to 60 min and was directly ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
abstract::Global blood flow (TBF), tumor vascular resistance, laser Doppler flow in superficial tumor areas, and mean arterial blood pressure were evaluated in rats bearing s.c. DS sarcomas. Measurements were performed before and after i.v. administration of rhTNF-alpha 2 or recombinant human lymphotoxin (rhLT) (1 mg/kg). Upon ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-04-15 00:00:00
abstract::The metabolism of the rat esophageal carcinogen N-nitrosomethylbenzylamine (NMBzA) was studied using microsomes prepared from liver and esophageal mucosa of untreated male Sprague-Dawley rats. NMBzA was extensively metabolized to benzaldehyde, benzyl alcohol, and formaldehyde by hepatic microsomes. The rate of metabol...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-08-01 00:00:00
abstract::In solid tumors, cancer cells subjected to ischemic conditions trigger distinct signaling pathways contributing to angiogenic stimulation and tumor development. Characteristic features of tumor ischemia include hypoxia and glucose deprivation, leading to the activation of hypoxia-inducible factor-1-dependent signaling...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-3235
更新日期:2007-07-15 00:00:00
abstract::Insulin-like growth factor (IGF) I has important growth regulatory functions in normal growth and development. IGF-I is also a mitogen for a number of cancer cell lines; however, its autocrine effect has not been well established. In this study, the expression of IGF-I, its receptor, and its major serum-binding protei...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-06-15 00:00:00
abstract::The metabolisms of two standard electron acceptors and a series of bioreductive antitumor compounds by purified rat and human DT-diaphorases (DTD) were compared. DTD was purified from rat liver cytosol and from Escherichia coli in which rat liver or human lung tumor DTD complementary DNA was expressed. Km and kcat val...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-06-15 00:00:00
abstract::The environmental contaminant 6-nitrochrysene (6-NC) has been shown to induce adenomas and adenocarcinomas in the colons of rats. The present study aimed at providing a better understanding of mechanisms that are responsible for this effect. Three female CD rats were injected i.p. with [3,4,9,10-3H]6-NC [9 mumol/rat (...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1996-05-01 00:00:00
abstract::In cancer cachexia both cardiac and skeletal muscle suffer an important protein mobilization as a result of increased proteolysis. Administration of the beta2-agonist formoterol to both rats and mice bearing highly cachectic tumors resulted in an important reversal of the muscle-wasting process. The anti-wasting effec...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-0425
更新日期:2004-09-15 00:00:00
abstract::Cell proliferation in 211 primary non-small cell lung carcinomas was assessed by using an immunostaining of proliferating cell nuclear antigen (PCNA) and a silver staining of argyrophilic nucleolar organizer region (Ag-NOR). More than 5% PCNA positive cells was designated PCNA(+), and less than 5% was PCNA(-). A mean ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-10-15 00:00:00
abstract::We estimated associations between polymorphisms in the gene encoding microsomal epoxide hydrolase (mEH) among 464 cases diagnosed with first occurrence of colorectal adenoma and 510 matched controls. In an analysis controlling only for the matching variables, we found little or no association between adenoma and mEH g...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-15 00:00:00
abstract::To determine the role of the transcription factor signal transducer and activator of transcription (STAT) 1 on endothelial cell function, human umbilical vein endothelial cells (HUVEC) were treated with IFN-gamma, a potent activator of STAT1. IFN-gamma inhibited cell growth and tube formation of HUVECs. Although the p...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3612
更新日期:2006-04-01 00:00:00
abstract::Previous studies have shown that among populations with a high rate of consanguinity, there is a significant increase in the prevalence of cancer. Single nucleotide polymorphism (SNP) array data (Affymetrix, 50K XbaI) analysis revealed long regions of homozygosity in genomic DNAs taken from tumor and matched normal ti...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5250
更新日期:2008-04-15 00:00:00
abstract::Untargeted effects of ionizing radiation (de novo effects in the unirradiated descendants or neighbors of irradiated cells) challenge widely held views about the mechanisms of radiation-induced DNA damage with implications for the health consequences of radiation exposures particularly in the context of the induction ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-0834
更新日期:2005-07-01 00:00:00
abstract::Focal adhesion kinase (FAK) and vascular endothelial growth factor receptor-3 (VEGFR-3) are protein tyrosine kinases that are overexpressed in human cancer and play an important role in survival signaling. In addition to its involvement with cell survival, VEGFR-3 is a primary factor in lymphatic angiogenesis. Because...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1661
更新日期:2006-02-01 00:00:00
abstract::Analyses of losses of heterozygosity and linkage studies have implicated a gene(s) on chromosome 17q in the genesis of sporadic and early-onset familial breast carcinomas, respectively. To define the critical region of 17q, we examined DNAs from a series of 20 sporadic breast carcinomas and corresponding blood samples...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-05-01 00:00:00
abstract::We know that the Yin Yang 1 protein (YY1) overexpression is positively and strongly correlated with the degree of malignancy of bone tumors. Therefore, we questioned whether we could influence cell invasiveness by deleting YY1 in human osteosarcoma cells (SaOs-2), as tested in Matrigel-coated filters and metastasis im...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-5582
更新日期:2008-03-15 00:00:00
abstract::Cyclin-dependent kinase 2 activated by cyclin E is involved in the initiation of DNA replication and other S phase functions. Consistent with this role, cyclin E protein accumulates at the G1-S phase transition and declines during early S phase. This profile of expression is the result of periodic transcription and ub...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-08-15 00:00:00
abstract::Although a majority of malignant testicular Leydig cell tumors induced in the mouse by chronic estrogenization remain dependent upon estrogen stimulation for growth during early transplant generations, we have observed tumors of two lines, no longer growth dependent upon estrogen, that regressed when hosts bearing pal...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-11-01 00:00:00
abstract::Paclitaxel is a standard-of-care chemotherapy for breast cancer, despite the increasing recognition of its poor effectiveness in the treatment of patients with advanced disease. Here, we report that adenovirus-type 5 E1A-mediated elevation of the miRNA-processing enzyme Dicer is sufficient to enhance paclitaxel sensit...
journal_title:Cancer research
pub_type: 杂志文章,收录出版
doi:10.1158/0008-5472.CAN-15-2555
更新日期:2016-07-01 00:00:00
abstract::Sputum samples obtained during the screening phase of a chemoprevention trial in heavy smokers were evaluated independently by trained cytotechnologists and classified for degree of cellular atypia according to the method of Saccommano et al. (G. Saccommano et al., Cancer (Phila.), 33: 256-270, 1974). The level of agr...
journal_title:Cancer research
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1990-02-15 00:00:00
abstract::In order to characterize the promoting activity of the peroxisome proliferator [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (WY-14,463), male F344 rats which received a single 150-mg/kg dose of diethylnitrosamine (DEN) were fed 0.1% WY-14,643 or 0.05% phenobarbital in the diet for 11, 22, or 54 wk. WY-14,6...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-06-15 00:00:00
abstract::Although the t(2;13)(q35;q14) translocation has been found in most cases of the pediatric cancer alveolar rhabdomyosarcoma, several cases have been reported with a variant t(1;13)(p36;q14) translocation. Our findings indicate that this t(1;13) rearranges PAX7 on chromosome 1 and fuses it to FKHR on chromosome 13. This...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-06-01 00:00:00
abstract::Head and neck squamous cell carcinomas (HNSCC) often metastasize to locoregional lymph nodes, and lymph node involvement represents one of the most important prognostic factors of poor clinical outcome. HNSCCs are remarkably lymphangiogenic and represent a clear example of a cancer that utilizes the lymphatic vasculat...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-3121
更新日期:2015-07-15 00:00:00
abstract::Hybridoma-derived monoclonal anti-colorectal carcinoma antibodies suppressed the growth of colorectal carcinoma in nude mice as evidenced by a lower incidence of tumors, a longer latency period, and a smaller volume of tumors in antibody-treated than in control animals. The growth-inhibiting properties of monoclonal a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-03-01 00:00:00
abstract::Lymphoid cell subpopulations infiltrating into autografts of methylcholanthrene-induced sarcomas in rats immunized with autologous tumor cells were identified in terms of immunohistochemical and cytofluorographic techniques using various monoclonal antibodies raised against different classes of rat lymphohemopoietic c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-09-01 00:00:00
abstract::Lung cancer is the leading cause of cancer death globally. An improved risk stratification strategy can increase efficiency of low-dose computed tomography (LDCT) screening. Here we assessed whether individual's genetic background has clinical utility for risk stratification in the context of LDCT screening. Based on ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-20-1237
更新日期:2021-01-20 00:00:00
abstract::Convection enhanced delivery (CED) is potentially a powerful method to improvethe targeting of macromolecules to the central nervous system by applying a pressure gradient to establish bulk flow through the brain interstitium during infusion. The purpose of the present study was to evaluate CED as a means to improve t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-11-15 00:00:00