Abstract:
:The chemotherapeutic agents doxorubicin (dox) or 5-fluorouracil (5FU) are used to treat cancer cells as they cause irreparable DNA damage, inducing these aberrant cells to undergo cell death. The mediator of this process is presumed to be in part the tumor suppressor p53 which regulates genes involved in DNA repair and cell death. When MCF-7 breast cancer cells are treated with these drugs, we observed that the level of p53 and the p53 negative regulator, Mdm2, increased, as seen by others. But contrary to some reports, we observed minimal phosphorylation of p53 at serine 15 in MCF-7 cells after drug treatment. Interestingly, we determined that there was differential regulation of the kinases ATM and Chk2 with the drug treatments, likely the cause for the lack of phosphorylation of p53. We found a dramatic drop in p53 DNA binding affinity for p21 and other gene response elements (RE) after drug treatment. To determine if the p53 that accumulated in the drug treated cells was functionally active, we monitored changes in the protein products of two p53-regulated genes following drug treatment with and without the addition of a p53-specific siRNA. In response to 5FU, both p21 and Mdm2 proteins increased and that increase was alleviated if a p53-specific siRNA was added. This effect was not seen with the addition of dox. Thus, the phosphorylation at serine 15 is not necessary for the functional activation of this transcription factor. We propose a new model for the regulation of p53, Mdm2, and MdmX after drug treatment.
journal_name
Cancer Biol Therjournal_title
Cancer biology & therapyauthors
Balmer MT,Katz RD,Liao S,Goodwine JS,Gal Sdoi
10.4161/cbt.29112subject
Has Abstractpub_date
2014-08-01 00:00:00pages
1000-12issue
8eissn
1538-4047issn
1555-8576pii
29112journal_volume
15pub_type
杂志文章abstract::Understanding the biology of breast cancer stem cells and trying new ways to obliterate these cells would be a key step in developing cures for breast cancer. The objective of this study was to investigate the effect of mutant TNFalpha on human breast cancer stem cells derived from MCF7 cell line under the characteriz...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.9.4885
更新日期:2007-09-01 00:00:00
abstract:PURPOSE:The sensitivity of lung cancer to gefitinib has been found to be associated with mutations at the tyrosine kinase domain of epidermal growth factor receptor (EGFR), yet similar observations are not available in other solid tumors. We recently identified mutations in the EGFR kinase domain in primary esophageal ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.2.2318
更新日期:2006-02-01 00:00:00
abstract::Many genes controlling cell proliferation and survival (those most important to cancer biology) are now known to be regulated specifically at the translational (RNA to protein) level. The internal ribosome entry site (IRES) provides a mechanism by which the translational efficiency of an individual or group of mRNAs c...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2015.1071729
更新日期:2015-01-01 00:00:00
abstract::More than a decade has passed since BRCA1, breast cancer tumor suppressor 1, was isolated by reverse genetics in 1994. Its molecular structure and potential function have been extensively studied; both mouse genetics and a cell culture system revealed that BRCA1 is a 220,240 kD nuclear phosphoprotein, it regulates tra...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.5.5.2845
更新日期:2006-05-01 00:00:00
abstract::Male germ cell tumors (GCTs) are a model for a curable solid tumor. GCTs can differentiate into mature teratomas. Embryonal carcinomas (ECs) represent the stem cell compartment of GCTs and are the malignant counterpart to embryonic stem (ES) cells. GCTs and EC cells are useful to investigate differentiation therapy an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.27821
更新日期:2014-04-01 00:00:00
abstract::The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is important in nasopharyngeal carcinoma (NPC) pathogenesis. Activated PI3K and its downstream target Akt are concernful signaling molecules and key survival factors involved in the control of cell proliferation, apoptosis and oncogenesis. The protein kinase A...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.4.7433
更新日期:2009-02-01 00:00:00
abstract:OBJECTIVE:Angiogenesis is one of the key processes in the development of malignant tumors. The vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) signaling pathway regulates branching angiogenesis in cancer. In this study, we analyzed the associations of VEGF/VEGFR-2 proteins and VEGFR-2 genetic va...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1537575
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Uterine malformation is a rare deformity in woman, and only a few cases concerning endometrial cancer arising in patients with congenital uterine anomalies have been reported. Herein, we present 3 cases of endometrial cancer with different congenital uterine anomalies, and review studies involving congenital...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.1080/15384047.2017.1281495
更新日期:2017-03-04 00:00:00
abstract:BACKGROUND:Although the prognosis for malignant gliomas is normally dismal, it's not infrequent in neurooncologist's experience to find cases with unusually prolonged survival. In order to understand what factors influence survival of high grade glioma patients, a cohort of 196 high (III-IV) grade glioma patients was i...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,多中心研究
doi:10.4161/cbt.8.18.9209
更新日期:2009-09-01 00:00:00
abstract::The irreversible ERBB1/2/4 inhibitor neratinib has been shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET, PDGFRα and mutant RAS proteins via autophagic degradation. Neratinib interacted in an additive to synergistic fashion with the approved PARP1 inhibitor niraparib to kill ov...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2018.1436024
更新日期:2018-06-03 00:00:00
abstract::Prostate cancer is the second leading cause of cancer-related deaths in men. Fatty acid synthase (FASN) is normally upregulated during human prostate cancer onset and metastatic progression and its expression positively correlates with the development of advanced metastatic disease. However, it remains unknown what mo...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.8.4447
更新日期:2007-08-01 00:00:00
abstract::The epidermal growth factor receptor (EGFR) is a central regulator of tumor progression in human cancers. Cetuximab is an anti-EGFR monoclonal antibody that has been approved for use in oncology. Despite clinical success the majority of patients do not respond to cetuximab and those who initially respond frequently ac...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.24342
更新日期:2013-06-01 00:00:00
abstract::Imatinib, an ABL tyrosine kinase inhibitor (TKI), has shown clinical efficacy against chronic myeloid leukemia (CML). However, a substantial number of patients develop resistance to imatinib treatment due to the emergence of clones carrying mutations in the protein BCR-ABL. The phosphoinositide 3 kinase (PI3K)/Akt/mam...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.26725
更新日期:2014-02-01 00:00:00
abstract::Prostate cancer is the second leading cause of cancer deaths among men. The availability of animal models that represent the events and factors that exist in the natural history and biology of human prostate cancer is essential in dealing with prostate cancer. In recent decades and presently, emphasis has been directe...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.12.18367
更新日期:2011-12-15 00:00:00
abstract:PURPOSE:Indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolic enzyme, plays an important role in immune escape through suppressing T-cell function. Since Vav1 signaling pathway regulates T cell homeostasis, this study was designed to test the hypothesis that IDO induces T-cell immunosuppression through inhibiting V...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.14.8882
更新日期:2009-07-01 00:00:00
abstract::SUMO (small ubiquitin-related modifier) represents a class of ubiquitin-like proteins that is conjugated, like ubiquitin, by a set of enzymes to cellular regulatory proteins, including oncogenes and tumor suppressor genes, that play key roles in the control of cell growth, differentiation and apoptosis. SUMO conjugati...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.74
更新日期:2002-05-01 00:00:00
abstract::KRAS mutational status has been shown to be a predictive biomarker of resistance to anti-EGFR monoclonal antibody (mAb) therapy in patients with metastatic colorectal cancer. We report the spectrum of KRAS mutation in 1506 patients with colorectal cancer and the identification and characterization of rare insertion mu...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.28550
更新日期:2014-06-01 00:00:00
abstract::Angiogenesis plays an essential role in tumor growth and metastasis and is a promising target for cancer therapy. We characterized the effects of selective CIAPIN1 inhibition on the angiogenesis gastric cancer cell line SGC7901 by stable transfection of CIAPIN1 siRNA. Our study has been shown that CIAPIN1 play the det...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.11.8795
更新日期:2009-06-01 00:00:00
abstract::The hypoxia-inducible factor 1alpha (HIF-1alpha) plays a major role in cancer progression. The role of this transcription factor in prostate cancer development and its transition to a metastatic and androgen refractory state remains to be elucidated. Previous reports have identified the existence of single nucleotide ...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.11.2091
更新日期:2005-11-01 00:00:00
abstract::Translocations and unique chromosome break points in melanoma will aid in the identification of the genes that are important in the neoplastic process. We have previously shown a unique translocation in malignant melanoma cells der(12)t(12;20). The transcription factor E2F1 maps to 20q11. Increased expression of E2F h...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.5.4.2512
更新日期:2006-04-01 00:00:00
abstract:PURPOSE:Optical coherence tomography (OCT) is a minimally invasive, depth-resolved imaging tool that can be implemented in a small diameter endoscope for imaging mouse models of colorectal cancer (CRC). In this study, we utilized ultrahigh resolution (UHR) OCT to serially image the lower colon of azoxymethane (AOM) tre...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.6.11.4852
更新日期:2007-11-01 00:00:00
abstract::A 67-year-old male presented with anasarca and persistent non-pruritic rash of lower extremities. Physical examination was positive for subcutaneous edema with a non-blanching rash of abdomen and lower extremities. Labs showed leukocytosis, lymphocytosis, anemia and thrombocytopenia. He also had acute kidney injury an...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2017.1394550
更新日期:2018-02-01 00:00:00
abstract::Hypermethylation at certain CpG-rich promoters and hypomethylation at repeated DNA sequences are very frequently found in cancers. We provide the first report that a DNA sequence (NBL2) can be either extensively hypermethylated or hypomethylated in cancer. Previously, it was shown that NBL2, a complex tandem DNA repea...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.4.4.1622
更新日期:2005-04-01 00:00:00
abstract::Our previous studies have demonstrated that atorvastatin induces autophagy in the androgen receptor negative prostate cancer PC3 cells through inhibition of geranylgeranyl biosynthesis [Parikh et al., Prostate. 70(9): 971-981 (2010)]. This study attempts to elucidate the molecular mechanism underlying atorvastatin-ind...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.12.8.15978
更新日期:2011-10-15 00:00:00
abstract::Krüppel-Like Factor 4 (KLF4) functions as a tumor suppressor in some cancers, but its molecular mechanism is not clear. Our recent study also showed that the expression of KLF4 is dramatically reduced in primary lung cancer tissues. To investigate the possible role of KLF4 in lung cancer, we stably transfected KLF4 in...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.9.7.11106
更新日期:2010-04-01 00:00:00
abstract::Mutationally activated and oncogenic versions of the ras genes were first identified in human tumors in 1982. This discovery prompted great interest in the development of anti-Ras strategies as novel, target-based approaches for cancer treatment. The three human ras genes represent the most frequently mutated oncogene...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.306
更新日期:2002-11-01 00:00:00
abstract::Sirtuins (SIRT) are nicotinamide adenine dinucleotide (NAD+) dependent deacetylases or ADP- ribosyl transferases (ARTs) that deacetylate lysine residues on various proteins regulating a variety of cellular and metabolic processes. These enzymes regulate metabolism, cell survival, differentiation and DNA repair. SIRT p...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.1080/15384047.2016.1139246
更新日期:2016-01-01 00:00:00
abstract::Ten years ago, a concerted effort from several labs resulted in the cloning of BRCA1, the first of two major hereditary breast/ovarian cancer predisposition genes. Since that time, BRCA1 has been linked to several key nuclear functions connected with the prevention of genomic instability. In particular, BRCA1 function...
journal_title:Cancer biology & therapy
pub_type: 杂志文章,评审
doi:10.4161/cbt.3.6.842
更新日期:2004-06-01 00:00:00
abstract::The development of microarray technology has allowed researchers to measure expression levels of thousands of genes simultaneously. Analysis of these data requires the best normalization and statistical approaches to account for the biological and technical variability inherent in the technique. To approach this probl...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.2.4.431
更新日期:2003-07-01 00:00:00
abstract::Although most researchers in biology tend to focus on very specific issues and questions about their preferred gene or pathway, sometimes we face situations in which nature presents us with a remarkable example of a gene with multiple functions. Since the discovery of the early growth response 1 (EGR1) gene in the mid...
journal_title:Cancer biology & therapy
pub_type: 杂志文章
doi:10.4161/cbt.8.20.9804
更新日期:2009-10-01 00:00:00