Abstract:
BACKGROUND:The AKT/mammalian target of rapamycin (mTOR) signaling pathway is regulated by 17α-estradiol (E2) signaling and mediates E2-induced proliferation and progesterone receptor (PgR) expression in breast cancer. METHODS AND RESULTS:Here we use deep sequencing analysis of previously published data from The Cancer Genome Atlas to demonstrate that expression of a key component of mTOR signaling, rapamycin-insensitive companion of mTOR (Rictor), positively correlated with an estrogen receptor-α positive (ERα+) breast tumor signature. Through increased microRNA-155 (miR-155) expression in the ERα+ breast cancer cells we demonstrate repression of Rictor enhanced activation of mTOR complex 1 (mTORC1) signaling with both qPCR and western blot. miR-155-mediated mTOR signaling resulted in deregulated ERα signaling both in cultured cells in vitro and in xenografts in vivo in addition to repressed PgR expression and activity. Furthermore we observed that miR-155 enhanced mTORC1 signaling (observed through western blot for increased phosphorylation on mTOR S2448) and induced inhibition of mTORC2 signaling (evident through repressed Rictor and tuberous sclerosis 1 (TSC1) gene expression). mTORC1 induced deregulation of E2 signaling was confirmed using qPCR and the mTORC1-specific inhibitor RAD001. Co-treatment of MCF7 breast cancer cells stably overexpressing miR-155 with RAD001 and E2 restored E2-induced PgR gene expression. RAD001 treatment of SCID/CB17 mice inhibited E2-induced tumorigenesis of the MCF7 miR-155 overexpressing cell line. Finally we demonstrated a strong positive correlation between Rictor and PgR expression and a negative correlation with Raptor expression in Luminal B breast cancer samples, a breast cancer histological subtype known for having an altered ERα-signaling pathway. CONCLUSIONS:miRNA mediated alterations in mTOR and ERα signaling establishes a new mechanism for altered estrogen responses independent of growth factor stimulation.
journal_name
Mol Cancerjournal_title
Molecular cancerauthors
Martin EC,Rhodes LV,Elliott S,Krebs AE,Nephew KP,Flemington EK,Collins-Burow BM,Burow MEdoi
10.1186/1476-4598-13-229subject
Has Abstractpub_date
2014-10-06 00:00:00pages
229issn
1476-4598pii
1476-4598-13-229journal_volume
13pub_type
杂志文章相关文献
Molecular Cancer文献大全abstract:BACKGROUND:Patients with familial adenomatous polyposis (FAP) are at increased risk for the development of colorectal cancer. Surgery and chemoprevention are the most effective means to prevent cancer development. Thymoquinone (TQ) is considered the main compound of the volatile Nigella sativa seed oil and has been rep...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-12-41
更新日期:2013-05-13 00:00:00
abstract:BACKGROUND:Interferon regulatory factor-1 (IRF-1) is a master regulator of IFN-γ induced gene transcription. Previously we have shown that IRF-1 transcriptionally induces CEACAM1 via an ISRE (Interferon-Stimulated Response Element) in its promoter. CEACAM1 pre-mRNA undergoes extensive alternative splicing (AS) generati...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-64
更新日期:2014-03-21 00:00:00
abstract::Cancer precursor/progenitor cells may initiate and sustain the growth of tumors, but evidence for their existence in human disease is indirect, relying on their in vitro properties and animal models. More directly, specific elimination of these rare cells from cancer patients should produce a delayed but progressive d...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-8-106
更新日期:2009-11-18 00:00:00
abstract:BACKGROUND:Zebrafish have been used as a vertebrate model to study human cancers such as melanoma, rhabdomyosarcoma, liver cancer, and leukemia as well as for high-throughput screening of small molecules of therapeutic value. However, they are just emerging as a model for human brain tumors, which are among the most de...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-015-0288-2
更新日期:2015-02-03 00:00:00
abstract:INTRODUCTION:ERBB3, one of the four members of the ErbB family of receptor tyrosine kinases, plays an important role in breast cancer etiology and progression. In the present study, we aimed to identify novel miRNAs that can potentially target ERBB3 and their biological functions. METHOD:The expression levels of miR-1...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-220
更新日期:2014-09-24 00:00:00
abstract:BACKGROUND:In high grade gliomas, 1p19q codeletion and EGFR amplification are mutually exclusive and predictive of dramatically different outcomes. We performed a microarray gene expression study of four high grade gliomas with 1p19q codeletion and nine with EGFR amplification, identified by CGH-array. RESULTS:The two...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-7-41
更新日期:2008-05-20 00:00:00
abstract::Cell lines are still a tool of choice for many fields of biomedical research, including oncology. Although cancer is a very complex disease, many discoveries have been made using monocultures of established cell lines. Therefore, the proper use of in vitro models is crucial to enhance our understanding of cancer. Ther...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-016-0565-8
更新日期:2016-12-19 00:00:00
abstract:BACKGROUND:Gefitinib is a tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) especially effective in tumors with activating EGFR gene mutations while EGFR wild-type non small cell lung cancer (NSCLC) patients at present do not benefit from this treatment.The primary site of gefitinib metabol...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-10-143
更新日期:2011-11-23 00:00:00
abstract:BACKGROUND:There is increasing evidence that circular RNAs (circRNAs) have significant regulatory roles in cancer development and progression; however, the expression patterns and biological functions of circRNAs in renal cell carcinoma (RCC) remain largely elusive. METHOD:Bioinformatics methods were applied to screen...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-021-01314-w
更新日期:2021-01-20 00:00:00
abstract::Cancer research has mainly focused on alterations of genes and proteins in cancer cells themselves that result in either gain-of-function in oncogenes or loss-of-function in tumour-suppressor genes. However, stromal variables within or around tumours, including blood and lymph vessels, stromal cells and various protei...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/1476-4598-5-43
更新日期:2006-10-06 00:00:00
abstract:BACKGROUND:Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily and is highly expressed in many human tumors including breast cancer. PPARgamma has been identified as a potential target for breast cancer therapy based on the fact that its activation by syn...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-7-90
更新日期:2008-12-05 00:00:00
abstract:BACKGROUND:CD44 is considered as 'a' metastasis associated gene, despite the fact that it is an umbrella term for a group of molecules produced from a single gene by alternative splicing. However, little consideration is given to the above in the literature of colorectal carcinomas as well as other tumour types, leadin...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-11-83
更新日期:2012-11-14 00:00:00
abstract:BACKGROUND:Hypermethylation of promotor CpG islands is a common mechanism that inactivates tumor suppressor genes in cancer. Genes belonging to the RASSF gene family have frequently been reported as epigenetically silenced by promotor methylation in human cancers. Two members of this gene family, RASSF1A and RASSF5A ha...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-11-40
更新日期:2012-06-13 00:00:00
abstract:BACKGROUND:Among women worldwide, breast cancer is the most commonly diagnosed cancer, and the second leading cause of cancer-related deaths. Improved understanding of breast tumourigenesis may facilitate the development of more effective therapies. Peroxisome proliferator-activated receptor (PPAR)γ is a transcription ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-015-0347-8
更新日期:2015-04-15 00:00:00
abstract:BACKGROUND:Neuroblastoma is responsible for 15% of all childhood cancer deaths. Despite advances in treatment and disease management, the overall 5-year survival rates remain poor in high-risk disease (25-40%). MiR-497 was previously identified by our laboratory as a member of a miRNA expression signature, predictive o...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-12-23
更新日期:2013-03-26 00:00:00
abstract:BACKGROUND:To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC). PATIENTS AND METHODS:We analyzed, prospectively, the expression of Smad1-8, by means of Ribonuclease Protection Assay in 48 primary, operable, oral SCC. In addition, 21 larynx, 10 orop...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-106
更新日期:2010-05-12 00:00:00
abstract:BACKGROUND:The clinical efficacy of camptothecin (CPT), a drug specifically targeting topoisomerase I (TopoI), is under evaluation for the treatment of malignant gliomas. Due to the high unresponsiveness of these tumours to chemotherapy, it would be very important to study the signalling network that drives camptotheci...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-7-66
更新日期:2008-08-11 00:00:00
abstract:BACKGROUND:Recently, it has been reported that long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2), a novel tumor suppressor, participates in regulating the carcinogenesis and suppresses tumor progression by sponging microRNAs (miRNAs). However, the expression and function of CASC2 in hepatocellular ...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-017-0702-z
更新日期:2017-07-17 00:00:00
abstract::Bortezomib is a novel anti-cancer agent which has shown promising activity in non-small lung cancer (NSCLC) patients. However, only a subset of patients respond to this treatment. We show that NSCLC cell lines are differentially sensitive to bortezomib, IC50 values ranging from 5 to 83 nM. The apoptosis-inducing poten...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-6-73
更新日期:2007-11-17 00:00:00
abstract:BACKGROUND:Sharing the common neuroectodermal origin, melanoma and neuroblastoma are tumors widely diffused among adult and children, respectively. Clinical prognosis of aggressive neuroectodermal cancers remains dismal, therefore the search for novel therapies against such tumors is warranted. Curcumin is a phytochemi...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-137
更新日期:2010-06-03 00:00:00
abstract:BACKGROUND:Alterations in lipid metabolism are inherent to the metabolic transformations that support tumorigenesis. The relationship between the synthesis, storage and use of lipids and their importance in cancer is poorly understood. The human group X secreted phospholipase A2 (hGX sPLA2) releases fatty acids (FAs) f...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-12-111
更新日期:2013-09-27 00:00:00
abstract:BACKGROUND:Alterations of chromosome 8 and hypomethylation of LINE-1 retrotransposons are common alterations in advanced prostate carcinoma. In a former study including many metastatic cases, they strongly correlated with each other. To elucidate a possible interaction between the two alterations, we investigated their...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-6-14
更新日期:2007-02-05 00:00:00
abstract:BACKGROUND:Atypical adenomatous hyperplasia (AAH) and squamous cell dysplasia (SCD) are associated with the development of malignant lesions in the lung. Accurate diagnosis of AAH and SCD could facilitate earlier clinical intervention and provide useful information for assessing lung cancer risk in human populations. D...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-78
更新日期:2014-04-05 00:00:00
abstract:BACKGROUND:Reovirus type 3 Dearing strain (ReoT3D) has an inherent propensity to preferentially infect and destroy cancer cells. The oncolytic activity of ReoT3D as a single agent has been demonstrated in vitro and in vivo against various cancers, including colon, pancreatic, ovarian and breast cancers. Its human safet...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-8-47
更新日期:2009-07-14 00:00:00
abstract:BACKGROUND:Metastatic renal cell carcinoma (RCC) remains the leading cause of mortality in patients with clear cell RCC arising from mutations in the von Hippel Lindau (VHL) tumor suppressor. Successful RCC tumor suppression by VHL requires the negative regulation of hypoxia inducible factor alpha (HIF alpha) protein a...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-5-66
更新日期:2006-12-01 00:00:00
abstract:INTRODUCTION:Tumor-initiating cells (TICs), aka "cancer stem cells", are believed to fuel tumors and to sustain therapy resistance and systemic metastasis. Breast cancer is the first human carcinoma in which a subpopulation of cells displaying a specific CD44+/CD24-/low/ESA+ antigenic phenotype was found to have TIC pr...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-13-213
更新日期:2014-09-12 00:00:00
abstract:BACKGROUND:Reactive oxygen species contribute to normal thyroid function. The NRF2 oxidative response pathway is frequently and constitutively activated in multiple tumor types, including papillary thyroid carcinoma (PTC). Genetic mechanisms underlying NRF2 pathway activation in PTC are not fully understood. Thus, we a...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-12-124
更新日期:2013-10-20 00:00:00
abstract:BACKGROUND:Emerging studies suggest that long non-coding RNAs (lncRNAs) play crucial roles in colorectal cancer (CRC). Here, we report a lncRNA, SATB2-AS1, which is specifically expressed in colorectal tissue and is significantly reduced in CRC. We systematically elucidated its functions and possible molecular mechanis...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/s12943-019-1063-6
更新日期:2019-09-06 00:00:00
abstract::Prostate cancer, the second most frequently diagnosed cancer in males worldwide, is estimated to be diagnosed in 1.1 million men per year. Introduction of PSA testing substantially improved early detection of prostate cancer, however it also led to overdiagnosis and subsequent overtreatment of patients with an indolen...
journal_title:Molecular cancer
pub_type: 杂志文章,评审
doi:10.1186/s12943-016-0523-5
更新日期:2016-05-18 00:00:00
abstract::Live animal imaging is becoming an increasingly common technique for accurate and quantitative assessment of tumor burden over time. Bioluminescence imaging systems rely on a bioluminescent signal from tumor cells, typically generated from expression of the firefly luciferase gene. However, previous reports have sugge...
journal_title:Molecular cancer
pub_type: 杂志文章
doi:10.1186/1476-4598-9-299
更新日期:2010-11-22 00:00:00