Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin.

Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Abstract Text:

Heidi M Sankala,Nitai C Hait,Steven W Paugh,Dai Shida,Sandrine ,Lynne W Elmore,Paul Dent,Sheldon Milstien,Sarah Spiegel,

Sphingosine-1-phosphate is a potent lipid mediator formed by phosphorylation of sphingosine, a metabolite of sphingolipids, catalyzed by two sphingosine kinase (SphK) isoenzymes, SphK1 and SphK2. Expression of SphK2, which is enriched in the nucleus of MCF7 human breast cancer cells, increased expression of the cyclin-dependent kinase inhibitor p21 but had no effect on p53 or its phosphorylation. The anticancer drug doxorubicin is known to increase p21 via p53-dependent and p53-independent mechanisms. Down-regulation of endogenous SphK2 with small interfering RNA targeted to unique mRNA sequences decreased basal and doxorubicin-induced expression of p21 without affecting increased expression of p53. Down-regulation of SphK2 also decreased G(2)-M arrest and markedly enhanced apoptosis induced by doxorubicin. Moreover, siSphK2 reduced doxorubicin-induced p21 expression in p53-inactivated MCF7 cells. Likewise, in human wild-type p53- and p21-expressing HCT116 colon carcinoma cells, as well as in p53-null counterparts, down-regulation of SphK2 markedly reduced p21 induction by doxorubicin. Knockdown of SphK2 sensitized HCT116 cells to apoptosis induced by doxorubicin with concomitant cleavage of poly(ADP-ribose) polymerase. Collectively, our results show that endogenous SphK2 is important for p53-independent induction of p21 expression by doxorubicin and suggest that SphK2 may influence the balance between cytostasis and apoptosis of human cancer cells.

Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Publishing Authors By Initials

HM Sankala,NC Hait,SW Paugh,D Shida,S ,LW Elmore,P Dent,S Milstien,S Spiegel,

For similar abstracts research abstracts see: abstracts research

PUBMED ID PMID:

MEDLINE DATE:

Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Cancer research

VOLUME: 67

Page Numbers: 10466-74

Journal Abbreviation: Cancer Res.

ISSN: 1538-7445

DAY: 1

MONTH: Nov

YEAR: 2007

Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Keywords Mesh Terms:

KEYWORDS:

MESH TERMS:

Chemical & Substance for Abstract: Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin. Information

Substance Name:

Registry Number:

Grant and Affiliation Information for Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin.

AFFILIATION: Department of Biochemistry and Molecular Biology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0614, USA.

Country: United States

AGENCY: United States NIAID

GRANT: T32AI007407

ACRONYM: AI

MEDLINETA: Cancer Res

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin Related Publications

• A longitudinal study of depression, pain, and stress as predictors of sleep disturbance among women with metastatic breast cancer.
• A rapid and sensitive method to measure secretion of sphingosine-1-phosphate.
• Association of coping style, pain, age and depression with fatigue in women with primary breast cancer.
• Autocrine and paracrine roles of sphingosine-1-phosphate.
• Ceramide kinase regulates growth and survival of A549 human lung adenocarcinoma cells.
• Diversity, nomenclature, and taxonomy of protists.
• Emotional expression and diurnal cortisol slope in women with metastatic breast cancer in supportive-expressive group therapy: a preliminary study.
• Evidence of dissociative amnesia.
• Formation of traveling waves in nematics due to material parameter ramps.
• Impact of sleep and sleep loss on neuroendocrine and metabolic function.
• Inherited endocrine diseases involving g proteins and g protein-coupled receptors.
• Involvement of sphingosine kinase 2 in p53-independent induction of p21 by the chemotherapeutic drug doxorubicin.
• Klebsiella rhinoscleromatis of the membranous nasal septum.
• Measurement of mammalian sphingosine-1-phosphate phosphohydrolase activity in vitro and in vivo.
• Measuring general practitioners' mental health competencies.
• Morphologic features in the regenerating liver--a comparative intravital, lightmicroscopical and ultrastructural analysis with focus on hepatic stellate cells.
• Protostelids from deciduous forests: first data from southwestern Europe.
• Regulation of fibroblast functions by lysophospholipid mediators: potential roles in wound healing.
• Shooting the messenger: oxidative stress regulates sphingosine-1-phosphate.
• Sphingosine 1-phosphate in neural signalling and function.
• Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases.
• Sphingosine-1-phosphate in allergic responses, asthma and anaphylaxis.
• Stress history and breast cancer recurrence.
• Structure and function of the human calcium-sensing receptor: insights from natural and engineered mutations and allosteric modulators.
• The abuse-related beliefs questionnaire for survivors of childhood sexual abuse.
• The cost-effectiveness and budget impact of competing therapies in hepatic encephalopathy - a decision analysis.
• The neural trance: a new look at hypnosis.
• [Effectiveness of triennial anti-influenza vaccination in French military during the 2003-2004 influenza season]
• [Indications for surgery from the viewpoints of surgeon and juror]
• [Legally effective consent with minors and incompetent patients]