Abstract:
:Protein kinase A (PKA) hyperactivation causes hereditary endocrine neoplasias; however, its role in sporadic epithelial cancers is unknown. Here, we show that heightened PKA activity in the mammary epithelium generates tumors. Mammary-restricted biallelic ablation of Prkar1a, which encodes for the critical type-I PKA regulatory subunit, induced spontaneous breast tumors characterized by enhanced type-II PKA activity. Downstream of this, Src phosphorylation occurs at residues serine-17 and tyrosine-416 and mammary cell transformation is driven through a mechanism involving Src signaling. The phenotypic consequences of these alterations consisted of increased cell proliferation and, accordingly, expansion of both luminal and basal epithelial cell populations. In human breast cancer, low PRKAR1A/high SRC expression defines basal-like and HER2 breast tumors associated with poor clinical outcome. Together, the results of this study define a novel molecular mechanism altered in breast carcinogenesis and highlight the potential strategy of inhibiting SRC signaling in treating this cancer subtype in humans.
journal_name
Oncogenejournal_title
Oncogeneauthors
Beristain AG,Molyneux SD,Joshi PA,Pomroy NC,Di Grappa MA,Chang MC,Kirschner LS,Privé GG,Pujana MA,Khokha Rdoi
10.1038/onc.2014.41subject
Has Abstractpub_date
2015-02-26 00:00:00pages
1160-73issue
9eissn
0950-9232issn
1476-5594pii
onc201441journal_volume
34pub_type
杂志文章相关文献
ONCOGENE文献大全abstract::c-Abl is a nuclear and cytoplasmic tyrosine kinase involved in a variety of cellular growth and differentiation processes. In contrast to its oncogenic counterparts, like BCR-Abl, c-Abl is not constitutively tyrosine phosphorylated and its catalytic activity is very low. Here we report tyrosine phosphorylation of endo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205017
更新日期:2001-12-06 00:00:00
abstract::MEMO1 (mediator of ErbB2-driven cell motility 1) regulates HER2-dependent cell migration. Increased MEMO1 expression is associated with cancer aggressiveness. Here, we found that MEMO1 is also involved in breast carcinogenesis via regulating insulin-like growth factor-I receptor-dependent signaling events. We showed t...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2012.327
更新日期:2013-06-27 00:00:00
abstract::Various factors and cellular components in the tumor microenvironment are key drivers associated with drug resistance in many cancers. Here, we analyzed the factors and molecular mechanisms involved in chemoresistance in patients with esophageal squamous cell carcinoma (ESCC). We found that interleukin 6 (IL6) derived...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2017.387
更新日期:2018-02-15 00:00:00
abstract::Amplification and overexpression of the E2F3 gene at 6p22 in human bladder cancer is associated with increased tumour stage, grade and proliferation index, and in prostate cancer E2F3 overexpression is linked to tumour aggressiveness. We first used small interfering RNA technology to confirm the potential importance o...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1209854
更新日期:2007-02-15 00:00:00
abstract::Type I interferon (IFN) enhances the transcription of the tumor suppressor gene p53. To elucidate the molecular mechanism mediating IFN-induced apoptosis, we analysed programmed cell death in response to type I (IFNalpha) or type II (IFNgamma) treatment in relation to p53 status. In two cell lines (MCF-7, SKNSH), IFNa...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1208204
更新日期:2005-01-20 00:00:00
abstract::The retinoblastoma (Rb) tumor suppressor gene and its close relatives p107 and p130 are best known for their function in the control of cell cycle progression. In recent years, however, a new role for these proteins has been emerging as they have been linked with regulation of terminal differentiation of many tissues ...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1203244
更新日期:1999-12-20 00:00:00
abstract::The exact functions of BRCA1 have not been fully described but it now seems apparent that it has roles in DNA damage repair, transcriptional regulation, cell cycle control and most recently in ubiquitylation. These functions of BRCA1 are most likely interdependent but this review will focus on the role of BRCA1 in rel...
journal_title:Oncogene
pub_type: 杂志文章,评审
doi:10.1038/sj.onc.1209872
更新日期:2006-09-25 00:00:00
abstract::In this study, we examined the role of the E-cadherin-repressed gene human Nanos1 (hNanos1) in tumor invasion process. First, our in vivo study revealed that hNanos1 mRNAs were overexpressed in invasive lung carcinomas. Moreover, hNanos1 was co-localized with MT1-MMP (membrane type 1-matrix metalloproteinase) in E-cad...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1211035
更新日期:2008-06-12 00:00:00
abstract::The angiogenic peptide adrenomedullin (ADM) has been implicated as a mediator of the increased risk of endometrial hyperplasia and cancer resulting from the use of tamoxifen for the treatment and prevention of breast cancer. ADM has been shown to be induced by tamoxifen in the endometrium and to be a growth factor for...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1205374
更新日期:2002-04-25 00:00:00
abstract::Clinical and epidemiological data support a role for human papilloma virus (HPV) type 16 in the pathogenesis of cervical carcinoma. The W12 cell line contains HPV16 sequences, predominantly as a high copy number episome, and is immortalised in vitro, but non-tumourigenic. A morphologically distinct sub-line of the par...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1990-04-01 00:00:00
abstract::The HER-2/neu proto-oncogene is frequently amplified or overexpressed in many different types of human cancers, a phenomenon that has been shown to correlate with shorter survival time and lower survival rate in ovarian cancer patients. We previously reported that increased HER-2/neu expression led to more severe mali...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1995-10-05 00:00:00
abstract::Although activating mutations of fibroblast growth factor receptor 3 (FGFR3) are frequent in bladder tumors, little information is available on their specific effects in urothelial cells or the basis for the observed mutation spectrum. We investigated the phenotypic and signaling consequences of three FGFR3 mutations ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.280
更新日期:2009-12-03 00:00:00
abstract::Transcriptomic screens in breast cancer cell lines have identified a protein named anterior gradient-2 (AGR2) as a potentially novel oncogene overexpressed in estrogen receptor (ER) positive tumours. As targeting the ER is responsible for major improvements in cure rates and prevention of breast cancers, we have evalu...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2010.228
更新日期:2010-08-26 00:00:00
abstract::While 25% of human cancers harbor oncogenic Ras mutations, such mutations are not found in astrocytomas. We have previously demonstrated that the activation of receptor tyrosine kinases expressed by malignant human astrocytoma cells and specimens results in functional upregulation of the Ras signalling pathway and inc...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1203105
更新日期:1999-12-09 00:00:00
abstract::p53 is involved in several DNA repair pathways. Some of these require the specific transactivation of p53-dependent genes and others involve direct interactions between the p53 protein and DNA repair associated proteins. Previously, we have shown that p53 acts directly in Base Excision Repair (BER) when assayed under ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204120
更新日期:2001-02-01 00:00:00
abstract::The c-Met receptor is a potential therapeutic target for non-small cell lung cancer (NSCLC). Signaling interactions between c-Met and the mutant epidermal growth factor receptor (EGFR) have been studied extensively, but signaling intermediates and biological consequences of lateral signaling to c-Met in EGFR wild-type...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.84
更新日期:2011-08-18 00:00:00
abstract::The short arm of chromosome 17 is one of the most frequently affected chromosomal regions in lung cancers, while there is solid evidence that the p53 gene at 17p13.1 is a target for frequent 17p deletions. In the present study, we re-evaluated 17p deletions in lung cancers by conducting a detailed analysis of the mini...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1202128
更新日期:1998-10-22 00:00:00
abstract::BALB/c mice heterozygous for Trp53 develop a high proportion of spontaneous mammary tumors, a phenotype distinct from other mouse strains. BALB/c-Trp53+/- female mice, thus, resemble the hereditary Li-Fraumeni syndrome (LFS) characterized by early-onset of breast cancer, even though LFS involves TP53 mutations, which ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.38
更新日期:2013-11-28 00:00:00
abstract::pp60c-src, a cellular tyrosine kinase homologous to the retroviral v-src oncogene, becomes transiently activated during mitosis. Activation is accompanied by phosphorylation of three sites in the amino-terminal regulatory domain of the protein, threonine 34, threonine 46 and serine 72. These sites can be phosphorylate...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1993-03-01 00:00:00
abstract::Growth factor receptor-mediated signal transduction has been implicated in conferring resistance to conventional chemotherapy on cancer cells. In this study, we delineated a pathway that involves HER2/PI-3K/Akt in mediating multidrug resistance in human breast cancer cells. We found that the cell lines that express bo...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1206394
更新日期:2003-05-22 00:00:00
abstract::MicroRNAs (miRNAs) as modulators of gene expression have been described to display both tumor-promoting and tumor-suppressive functions. Although their role has been studied in different tumor types, little is known about how they regulate nuclear factor κB (NF-κB) signaling in breast cancer. Here, we performed an unb...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2011.571
更新日期:2012-09-13 00:00:00
abstract::Hec1 (highly expressed in cancer 1) or Nek2 (NIMA-related kinase 2) is often overexpressed in cancers with poor prognosis. Both are critical mitotic regulators, and phosphorylation of Hec1 S165 by Nek2 is required for proper chromosome segregation. Therefore, inactivation of Hec1 and Nek2 by targeting their interactio...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2014.67
更新日期:2015-03-05 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the western countries and is currently incurable due, in part, to difficulty in eliminating the leukemia cells protected by stromal microenvironment. Based on previous observations that CLL cells exhibit mitochondrial dysfunction and altered lipid...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2016.103
更新日期:2016-10-27 00:00:00
abstract::The marine alkaloid ascididemin (ASC) was shown to exert cytotoxicity even against multidrug-resistant cancer cells. Here, we address the signaling pathways utilized by ASC to trigger apoptosis in Jurkat leukemia T cells. We show that ASC (0.5-20 microM) induces a mitochondrial pathway that requires the activation of ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1207281
更新日期:2004-02-26 00:00:00
abstract::Previous work has demonstrated that E2F proteins regulate the expression of various genes encoding proteins essential for DNA replication and cell-cycle progression. E2F1 in particular is required for the initial entry to the cell cycle from a quiescent state and is required for the activation of other E2F genes. Othe...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2008.55
更新日期:2008-07-10 00:00:00
abstract::Previous studies have demonstrated that activation of Kit by stem cell factor (SCF), its natural ligand, or by gain-of-function point mutation in its intracellular domain, confers significant protection against apoptosis induced by growth factor deprivation or radiation. However, the effects of Kit activation on the c...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/sj.onc.1204877
更新日期:2001-10-11 00:00:00
abstract::Hedgehog pathway activity has been demonstrated in malignant glioma. However, its role in tumor growth has not been determined. Here we demonstrate that pharmacological inhibition of the Hedgehog pathway in established orthotopic malignant glioma xenografts confers a survival advantage. Pathway inhibition is measured ...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2009.208
更新日期:2009-10-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) are a kind of adult stem cells that can be isolated easily from bone marrow, adipose tissue, umbilical cord and many other tissues. MSCs have been shown to specifically migrate to inflammatory sites, including tumors, and hold great promise as tumor-specific vectors to deliver antitumor a...
journal_title:Oncogene
pub_type: 杂志文章
doi:10.1038/onc.2013.458
更新日期:2014-10-16 00:00:00
abstract::Within the superfamily of ras-related GTP-binding proteins, only ras itself has been shown to act as an oncogene. Seven other proteins, however, have greater than 50% amino acid identity to ras and one of them, rap1A, has been shown to interact with the ras GTPase activating protein, ras-GAP, and to inhibit ras functi...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1994-03-01 00:00:00
abstract::The v-myb oncogene of the avian myeloblastosis virus encodes a nuclear protein, p48v-myb, which binds to DNA in a sequence-specific manner. We have used wild type and mutant forms of this protein expressed in E. coli to study the protein and DNA determinants for sequence-specific DNA-binding. We have shown that only t...
journal_title:Oncogene
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00