当前位置： SCI文献检索 > BRITISH JOURNAL OF CANCER期刊下所有文献 > A novel form of constitutively active farnesylated Akt1 prevents mammary epithelial cells from anoikis and suppresses chemotherapy-induced apoptosis.

A novel form of constitutively active farnesylated Akt1 prevents mammary epithelial cells from anoikis and suppresses chemotherapy-induced apoptosis.

Abstract：

:Protein kinase B/Akt has been described as a central mediator of anti-apoptotic signals transduced by the PI3 kinase. Although the role of Akt in the suppression of apoptosis is well elucidated, a potential function of Akt in tumorigenesis and chemoresistance is less intensively documented. In this study, we describe the construction of a novel form of constitutively active Akt1, which relies on the deletion of its pleckstrin homology domain and the insertion of a C-terminal farnesylation sequence. Stable cell lines were generated with MCF10A mammary epithelial cells and A549 human NSCLC cells expressing constitutively active Akt1. Enigneered MCF10A cells were rendered resistant towards apoptosis resulting from loss of cellular substrate attachment (anoikis). We investigated the chemosensitivity of A549 cells expressing farnesylated Akt vs control cells. A profoundly decreased sensitivity towards Mitoxantrone and cisplatin was observed in cells expressing farnesylated Akt. No significant difference in sensitivity however was observed upon treatment with cell cycle specific chemotherapeutic agents like paclitaxel. Our data suggest, that Akt is a central mediator in the suppression of anoikis and modulation of chemotherapy-induced apoptosis. Therefore it represents a promising target for small molecule inhibitors to shift the apoptotic threshold in cancer cells after treatment with standard chemotherapy.

journal_name

Br J Cancer

journal_title

British journal of cancer

authors

Schmidt M,Hövelmann S,Beckers TL

doi

10.1038/sj.bjc.6600566

subject

Has Abstract

pub_date

2002-10-07 00:00:00

pages

924-32

issue

8

eissn

0007-0920

issn

1532-1827

journal_volume

87

pub_type

杂志文章

相关文献

BRITISH JOURNAL OF CANCER文献大全
  • CYP1B1 expression is induced by docetaxel: effect on cell viability and drug resistance.

    abstract：:The cytochrome P450 CYP1B1 is consistently overexpressed in tumour cells as compared to their normal counterparts, but its precise role in drug resistance is yet to be defined. It has been reported that transfection of CYP1B1 results in increased resistance to docetaxel in V79 cells (McFadyen et al, 2001). In this stu...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6604195

    authors： Martinez VG,O'Connor R,Liang Y,Clynes M

    更新日期：2008-02-12 00:00:00

  • Expression of laminin 5-γ2 chain in cutaneous squamous cell carcinoma and its role in tumour invasion.

    abstract：BACKGROUND:Laminin-5 (Ln5), a heterotrimer composed of three chains (α3, β3, and γ2), is a major component of the basement membrane in most adult tissues. One of the chains, Ln5-γ2, is a marker of invasive tumours because it is frequently expressed as a monomer in malignant tumours. Recent studies from our laboratories...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2011.283

    authors： Hamasaki H,Koga K,Aoki M,Hamasaki M,Koshikawa N,Seiki M,Iwasaki H,Nakayama J,Nabeshima K

    更新日期：2011-09-06 00:00:00

  • Resistance to 4-(9-acridinylamino) methanesulphon-m-anisidide (m-AMSA) in human myeloid leukaemia.

    abstract：:Sublines of a human myeloid leukaemia cell line, KBM-3, with increasing degrees of resistance to the antileukaemic agent 4'-(9-acridinlylamino) methanesulphon-m-anisidide (m-AMSA) were evaluated for their response to this drug using a clonogenic assay to measure cell survival and alkaline elution to assess m-AMSA indu...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1990.11

    authors： Skinner WL,Murray D,Kohli V,Beran M,McCredie KB,Freireich EJ,Andersson BS

    更新日期：1990-01-01 00:00:00

  • Chromosome complement and SV40 transformation of cells from patients susceptible to malignant disease.

    abstract：:A comparative study has been made of fibroblasts obtained from patients with differing susceptibilities to malignant disease, both with respect to their chromosome complements and their transformation with SV40 virus. Fibroblasts from 2 Bloom's syndrome patients were found not to have raised SV40 transformation rates ...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1977.235

    authors： Webb T,Harding M

    更新日期：1977-11-01 00:00:00

  • Glutathione S-transferase activity and isoenzyme distribution in ovarian tumour biopsies taken before or after cytotoxic chemotherapy.

    abstract：:A study involving the measurement of glutathione S-transferase activities and isoenzyme distributions in human ovarian tumours has been carried out. These tumours have been obtained either at initial debulking surgery, prior to cytotoxic chemotherapy, or at second look laparotomy following chemotherapy. The response r...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1992.389

    authors： Murphy D,McGown AT,Hall A,Cattan A,Crowther D,Fox BW

    更新日期：1992-11-01 00:00:00

  • Growth of human tumour cell colonies from biopsies using two soft-agar techniques.

    abstract：:Two techniques for growing colonies of human tumour cells in soft agar have been applied to cell suspensions derived from fresh tumour tissue from 48 patients. Colonies were obtained in 31 cases, with plating efficiencies between 0.01 and 15%. In 11 cases the plating efficiencies were 1% or above. There was evidence t...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1978.165

    authors： Courtenay VD,Selby PJ,Smith IE,Mills J,Peckham MJ

    更新日期：1978-07-01 00:00:00

  • Epidemiological investigations on neuroblastomas in Denmark 1943-1980.

    abstract：:During the period 1943-1980 a significant increase in the incidence of neuroblastoma was seen in Denmark. The incidence increased from a level corresponding to that in Finland to a level corresponding to that in the USA, and the increase appears to be continuing. The increase relates to children aged under 5 years, an...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1986.270

    authors： Carlsen NL

    更新日期：1986-12-01 00:00:00

  • Rab25 as a tumour suppressor in colon carcinogenesis.

    abstract：:Recent investigations have increasingly focussed attention on the roles of intracellular vesicle trafficking in the regulation of epithelial polarity and transformation. Rab25, an epithelial-specific member of the Rab family of small GTPases, has been associated with several epithelial cancers. Whereas Rab25 overexpre...

    journal_title：British journal of cancer

    pub_type： 杂志文章,评审

    doi：10.1038/sj.bjc.6605983

    authors： Goldenring JR,Nam KT

    更新日期：2011-01-04 00:00:00

  • Nutrient stress alters the glycosylation status of LGR5 resulting in reduced protein stability and membrane localisation in colorectal tumour cells: implications for targeting cancer stem cells.

    abstract：BACKGROUND:LGR5 is an important marker of intestinal stem cells and performs its vital functions at the cell membrane. Despite the importance of LGR5 to both normal and cancer stem cell biology, it is not known how microenvironmental stress affects the expression and subcellular distribution of the protein. METHODS:Nu...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2015.4

    authors： Morgan RG,Molnár E,Jones RF,Collard TJ,Lane JD,Greenhough A,Paraskeva C,Williams AC

    更新日期：2015-02-17 00:00:00

  • Germline mutations of the INK4a-ARF gene in patients with suspected genetic predisposition to melanoma.

    abstract：:Germline anomalies of the INK4a-ARF and Cdk4 genes were sought in a series of 89 patients suspected of having a genetic predisposition to melanoma. Patients were selected based on the following criteria: (a) familial melanoma (23 cases), (b) multiple primary melanoma (MPM; 18 cases), (c) melanoma and additional unrela...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6601503

    authors： Soufir N,Lacapere JJ,Bertrand G,Matichard E,Meziani R,Mirebeau D,Descamps V,Gérard B,Archimbaud A,Ollivaud L,Bouscarat F,Baccard M,Lanternier G,Saïag P,Lebbé C,Basset-Seguin N,Crickx B,Cave H,Grandchamp B

    更新日期：2004-01-26 00:00:00

  • Delay in referral of oropharyngeal squamous cell carcinoma to secondary care correlates with a more advanced stage at presentation, and is associated with poorer survival.

    abstract：:Squamous carcinoma of the oropharynx presents with symptoms common to many benign diseases, and this can cause delay in referral to secondary care. We investigate delay in referral, defining this as the time from symptom-onset to date of general practitioners referral letter to secondary care, and the effect of that d...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6603044

    authors： Pitchers M,Martin C

    更新日期：2006-04-10 00:00:00

  • Effective inhibition by low dose aminoglutethimide of peripheral aromatization in postmenopausal breast cancer patients.

    abstract：:Aminoglutethimide without glucocorticoid has been shown to be a clinically effective treatment for postmenopausal breast cancer in low dosage (250 mg day-1). The mechanism of action of this approach is thought to be the inhibition of peripheral aromatase, the enzyme which converts androstenedione to oestrone. The acti...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1985.144

    authors： Dowsett M,Santner SJ,Santen RJ,Jeffcoate SL,Smith IE

    更新日期：1985-07-01 00:00:00

  • A phase I dose escalation study of BIBW 2992, an irreversible dual inhibitor of epidermal growth factor receptor 1 (EGFR) and 2 (HER2) tyrosine kinase in a 2-week on, 2-week off schedule in patients with advanced solid tumours.

    abstract：:To assess tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical activity of the dual epidermal growth factor receptor (EGFR) 1 and 2 (HER2) tyrosine kinase inhibitor BIBW 2992. An escalating schedule of once-daily (OD) BIBW 2992 for 14 days followed by 14 days off medication was explored. Thirty-eigh...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6604108

    authors： Eskens FA,Mom CH,Planting AS,Gietema JA,Amelsberg A,Huisman H,van Doorn L,Burger H,Stopfer P,Verweij J,de Vries EG

    更新日期：2008-01-15 00:00:00

  • Competing mortality in patients diagnosed with bladder cancer: evidence of undertreatment in the elderly and female patients.

    abstract：BACKGROUND:Bladder cancer (BC) predominantly affects the elderly and is often the cause of death among patients with muscle-invasive disease. Clinicians lack quantitative estimates of competing mortality risks when considering treatments for BC. Our aim was to determine the bladder cancer-specific mortality (CSM) rate ...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2013.106

    authors： Noon AP,Albertsen PC,Thomas F,Rosario DJ,Catto JW

    更新日期：2013-04-16 00:00:00

  • Bone metastases in childhood renal tumours.

    abstract：:Analysis of data from 1434 children with primary renal tumours revealed 57 who developed bone metastases. Of these, 54 were initially recorded as nephroblastoma. Fifty-two of the 57 cases were reviewed histologically, and only 18 were found to be Wilms' tumours. Twenty-three were classified as "Bone-Metastasizing Rena...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1980.163

    authors： Marsden HB,Lennox EL,Lawler W,Kinnier-Wilson LM

    更新日期：1980-06-01 00:00:00

  • The impact of antigen density and antibody affinity on antibody-dependent cellular cytotoxicity: relevance for immunotherapy of carcinomas.

    abstract：:Antibody-dependent cellular cytotoxicity (ADCC) is considered to be the major mechanism through which tumour cells, upon treatment with anti-tumour MAbs, are eliminated in vivo. However, the relative importance of various parameters that influence the efficacy of ADCC is unclear. Here we present in vitro data on the i...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1998.518

    authors： Velders MP,van Rhijn CM,Oskam E,Fleuren GJ,Warnaar SO,Litvinov SV

    更新日期：1998-08-01 00:00:00

  • The impact of genetic counselling on risk perception in women with a family history of breast cancer.

    abstract：:Women with a family history of breast cancer generally self-refer because they have a feeling that their risk is high. However, they have, in general, only a hazy notion of the population risk of breast cancer and their own risk in relation to this. It is probable that they are helped by genetic counselling and, if at...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1994.423

    authors： Evans DG,Blair V,Greenhalgh R,Hopwood P,Howell A

    更新日期：1994-11-01 00:00:00

  • Lack of correlation between in vivo rejection of syngeneic fibrosarcomas and in vitro non-specific macrophage cytotoxicity.

    abstract：:Two transplantable, highly immunogenic syngeneic C57BL fibrosarcomas, FS1 and FS6, were shown to have tumour-specific rejection antigens, as shown by excision of the primary tumours and i.p. or i.m. injection of graded doses of the specific and unrelated tumour cells. I.p. challenge with tumour cells induced a large a...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1978.253

    authors： Evans R,Booth CG,Spencer F

    更新日期：1978-11-01 00:00:00

  • Early mortality from colorectal cancer in England: a retrospective observational study of the factors associated with death in the first year after diagnosis.

    abstract：BACKGROUND:The United Kingdom performs poorly in international comparisons of colorectal cancer survival with much of the deficit owing to high numbers of deaths close to the time of diagnosis. This retrospective cohort study investigates the patient, tumour and treatment characteristics of those who die in the first y...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2012.585

    authors： Downing A,Aravani A,Macleod U,Oliver S,Finan PJ,Thomas JD,Quirke P,Wilkinson JR,Morris EJ

    更新日期：2013-02-19 00:00:00

  • The association between population-based treatment guidelines and adjuvant therapy for node-negative breast cancer. British Columbia/Ontario Working Group.

    abstract：:This study evaluated the impact of province-wide treatment guidelines on consistency of adjuvant therapy for node-negative breast cancer. A retrospective population-based cohort study was conducted in the Canadian provinces of British Columbia, which has province-wide guidelines, and Ontario, which does not. All eligi...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1997.262

    authors： Sawka C,Olivotto I,Coldman A,Goel V,Holowaty E,Hislop TG

    更新日期：1997-01-01 00:00:00

  • MicroRNA in lung cancer.

    abstract：:MicroRNAs (miRNAs) are small non-protein-coding RNAs that function as endogenous negative gene regulators. Dysfunctions of miRNAs are frequently found in malignancies, including lung cancer. In this review, we summarise the current understanding of miRNAs in lung cancer tumourigenesis, and highlight their potential in...

    journal_title：British journal of cancer

    pub_type： 杂志文章,评审

    doi：10.1038/sj.bjc.6605901

    authors： Lin PY,Yu SL,Yang PC

    更新日期：2010-10-12 00:00:00

  • Importance of extensive staging in patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma.

    abstract：:Lymphoma of the mucosa-associated lymphoid tissue (MALT) type usually arises in MALT acquired through chronic antigenic stimulation triggered by persistent infection and/or autoimmune processes. Due to specific ligand-receptor interactions between lymphoid cells and high-endothelial venules of MALT, both normal and ne...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1054/bjoc.2000.1308

    authors： Raderer M,Vorbeck F,Formanek M,Osterreicher C,Valencak J,Penz M,Kornek G,Hamilton G,Dragosics B,Chott A

    更新日期：2000-08-01 00:00:00

  • Rural and urban differences in stage at diagnosis of colorectal and lung cancers.

    abstract：:There is evidence that patients living in outlying areas have poorer survival from cancer. This study set out to investigate whether they have more advanced disease at diagnosis. Case notes of 1323 patients in north and northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed....

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1054/bjoc.2000.1708

    authors： Campbell NC,Elliott AM,Sharp L,Ritchie LD,Cassidy J,Little J

    更新日期：2001-04-06 00:00:00

  • Dietary induction of NQO1 increases the antitumour activity of mitomycin C in human colon tumours in vivo.

    abstract：:The bioreductive antitumour agent, mitomycin C (MMC), requires activation by reductive enzymes like NAD(P)H:quinone oxidoreductase 1 (NQO1). We used a novel approach to increase MMC efficacy by selectively inducing NQO1 in tumour cells in vivo. CD-1 nude mice were implanted with HCT116 cells, and fed control diet or d...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6602171

    authors： Begleiter A,Leith MK,Thliveris JA,Digby T

    更新日期：2004-10-18 00:00:00

  • Altered expression of topoisomerase IIalpha contributes to cross-resistant to etoposide K562/MX2 cell line by aberrant methylation.

    abstract：:KRN 8602 (MX2) is a novel morpholino anthracycline derivative having the chemical structure 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. To investigate the mechanisms of resistance to MX2, we established an MX2-resistant phenotype (K562/MX2) of the human myelogeneous leukaemia cell line (K56...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6602498

    authors： Asano T,Nakamura K,Fujii H,Horichi N,Ohmori T,Hasegawa K,Isoe T,Adachi M,Otake N,Fukunaga Y

    更新日期：2005-04-25 00:00:00

  • Aldehyde dehydrogenase 3A1 associates with prostate tumorigenesis.

    abstract：BACKGROUND:Accumulating evidence demonstrates high levels of aldehyde dehydrogense (ALDH) activity in human cancer types, in part, because of its association with cancer stem cells. Whereas ALDH1A1 and ALDH7A1 isoforms were reported to associate with prostate tumorigenesis, whether other ALDH isoforms are associated wi...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2014.201

    authors： Yan J,De Melo J,Cutz JC,Aziz T,Tang D

    更新日期：2014-05-13 00:00:00

  • Comparison of nuclear texture analysis and image cytometric DNA analysis for the assessment of dysplasia in Barrett's oesophagus.

    abstract：BACKGROUND:Dysplasia is a marker of cancer risk in Barrett's oesophagus (BO), but this risk is variable and diagnosis is subject to inter-observer variability. Cancer risk in BO is increased when chromosomal instability is present. Nucleotyping (NT) is a new method that uses high-resolution digital images of nuclei to ...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2011.353

    authors： Dunn JM,Hveem T,Pretorius M,Oukrif D,Nielsen B,Albregtsen F,Lovat LB,Novelli MR,Danielsen HE

    更新日期：2011-10-11 00:00:00

  • Cell kinetic analysis of murine squamous cell carcinomas: a comparison of single versus double labelling using flow cytometry and immunohistochemistry.

    abstract：:The study was originally set up to measure accurate cell kinetic parameters in two murine squamous cell carcinomas (scc) for comparison with radiobiological data on proliferation during radiotherapy. The tumours, AT84 and AT478, were both moderately well differentiated aneuploid scc. In the course of the study, severa...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.1993.487

    authors： Schultz-Hector S,Begg AC,Hofland I,Kummermehr J,Sund M

    更新日期：1993-12-01 00:00:00

  • Methylation status of oestrogen receptor-alpha gene promoter sequences in human ovarian epithelial cell lines.

    abstract：:We have determined the methylation status of the CpG island of the oestrogen receptor alpha gene in seven human ovarian cell lines. Cell lines expressing oestrogen receptor alpha showed no evidence of hypermethylation. In three of four cell lines that produced no detectable oestrogen receptor alpha protein, hypermethy...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/sj.bjc.6600028

    authors： O'Doherty AM,Church SW,Russell SE,Nelson J,Hickey I

    更新日期：2002-01-21 00:00:00

  • Population-based cancer incidence in Sikkim, India: report on ethnic variation.

    abstract：BACKGROUND:A Population-Based Cancer Registry (PBCR) was set up in Sikkim (a state in the North Eastern India) in 2003. We examined incidence rates by ethnic groups from 2003-2008. METHODS:Age-adjusted incidence rates (AARs) per 100,000 person-years were calculated by direct method using the world standard population,...

    journal_title：British journal of cancer

    pub_type： 杂志文章

    doi：10.1038/bjc.2011.598

    authors： Verma Y,Pradhan PK,Gurung N,Sapkota SD,Giri P,Sundas P,Bhattarai BN,Nadayil D,Ramnath T,Nandakumar A

    更新日期：2012-02-28 00:00:00