Stimulation of mitochondrial activity by p43 overexpression induces human dermal fibroblast transformation.

Abstract:

:Mitochondrial dysfunctions are frequently reported in cancer cells, but their direct involvement in tumorigenesis remains unclear. To understand this relation, we stimulated mitochondrial activity by overexpression of the mitochondrial triiodothyronine receptor (p43) in human dermal fibroblasts. In all clones, this stimulation induced morphologic changes and cell fusion in myotube-like structures associated with the expression of several muscle-specific genes (Myf5, desmin, connectin, myosin, AchRalpha). In addition, these clones displayed all the in vivo and in vitro features of cell transformation. This phenotype was related to an increase in c-Jun and c-Fos expression and extinction of tumor suppressor gene expression (p53, p21WAF1, Rb3). Lastly, reactive oxygen species (ROS) production was increased in positive correlation to the stimulation of mitochondrial activity. The direct involvement of mitochondrial activity in this cell behavior was studied by adding chloramphenicol, an inhibitor of mitochondrial protein synthesis, to the culture medium. This inhibition resulted in partial restoration of the normal phenotype, with the loss of the ability to fuse, a strong decrease in muscle-specific gene expression, and potent inhibition of the transformed phenotype. However, expression of tumor suppressor genes was not restored. Similar results were obtained by using N-acetylcysteine, an inhibitor of ROS production. These data indicate that stimulation of mitochondrial activity in human dermal fibroblasts induces cell transformation through events involving ROS production.

journal_name

Cancer Res

journal_title

Cancer research

authors

Grandemange S,Seyer P,Carazo A,Bécuwe P,Pessemesse L,Busson M,Marsac C,Roger P,Casas F,Cabello G,Wrutniak-Cabello C

doi

10.1158/0008-5472.CAN-04-3652

subject

Has Abstract

pub_date

2005-05-15 00:00:00

pages

4282-91

issue

10

eissn

0008-5472

issn

1538-7445

pii

65/10/4282

journal_volume

65

pub_type

杂志文章
  • Inhibition of c-Jun-N-terminal-kinase sensitizes tumor cells to CD95-induced apoptosis and induces G2/M cell cycle arrest.

    abstract::Loss of susceptibility to apoptosis signals is a crucial step in carcinogenesis. Therefore, sensitization of tumor cells to apoptosis is a promising therapeutic strategy. c-Jun-N-terminal-kinases (JNK) have been implicated in stress-induced apoptosis, but may also contribute to survival signaling. Here we show that CD...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-04-2618

    authors: Kuntzen C,Sonuc N,De Toni EN,Opelz C,Mucha SR,Gerbes AL,Eichhorst ST

    更新日期:2005-08-01 00:00:00

  • The EWS protein is dispensable for Ewing tumor growth.

    abstract::EWS encodes a ubiquitously expressed RNA binding protein with largely unknown function. In Ewing sarcoma family tumors (EFT), one allele is rearranged with an ETS gene. This is the first description of an EFT with a complete EWS deficiency in the presence of two copies of a rearranged chromosome 22 carrying an interst...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kovar H,Jug G,Hattinger C,Spahn L,Aryee DN,Ambros PF,Zoubek A,Gadner H

    更新日期:2001-08-15 00:00:00

  • SMAC mimetics sensitize nonsteroidal anti-inflammatory drug-induced apoptosis by promoting caspase-3-mediated cytochrome c release.

    abstract::Nonsteroidal anti-inflammatory drugs (NSAID) are effective in suppressing the formation of colorectal tumors. However, the mechanisms underlying the antineoplastic effects of NSAIDs remain unclear. The effects of NSAIDs are incomplete, and resistance to NSAIDs is often developed. Growing evidence has indicated that th...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-5242

    authors: Bank A,Wang P,Du C,Yu J,Zhang L

    更新日期:2008-01-01 00:00:00

  • Placenta growth factor gene expression is induced by hypoxia in fibroblasts: a central role for metal transcription factor-1.

    abstract::Placenta growth factor (PlGF) is a mitogen for endothelial cells that can potentiate the growth and permeabilizing effects on endothelium of vascular endothelial growth factor. Here we report that hypoxia induces the expression of both PlGF mRNA and protein in immortalized/transformed mouse embryonic fibroblasts (mEFs...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Green CJ,Lichtlen P,Huynh NT,Yanovsky M,Laderoute KR,Schaffner W,Murphy BJ

    更新日期:2001-03-15 00:00:00

  • Rapid release of intracellular galectin-3 from breast carcinoma cells by fetuin.

    abstract::Galectin-3, a beta-galactoside binding protein, plays a significant role in cell to extracellular matrix interactions. Despite its extracellular expression, the precise physiological mechanisms that trigger its release from the intracellular milieu have not been characterized. The present analyses were, therefore, don...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Zhu WQ,Ochieng J

    更新日期:2001-03-01 00:00:00

  • Somatic Engineering of Oncogenic Chromosomal Rearrangements: A Perspective.

    abstract::The ability to engineer specific mutations in mice has proven essential to advancing our understanding of the molecular basis of cancer. Chromosomal rearrangements, a common and clinically relevant class of cancer-causing mutations, have however remained difficult to faithfully recapitulate in vivo The development of ...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-16-0726

    authors: Maddalo D,Ventura A

    更新日期:2016-09-01 00:00:00

  • Monoclonal antibodies to cell surface antigens shared by chemically induced mouse bladder carcinomas.

    abstract::Rats were immunized with cultured cells from chemically induced transitional cell carcinomas of the mouse urinary bladder, and their spleen cells were hybridized with NS-1 mouse myeloma cells. Following initial screening of antibodies made by hybridoma clones, the tissue distribution of antigens defined by the antibod...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Hellström I,Hellström KE,Rollins N,Lee VK,Hudkins KL,Nepom GT

    更新日期:1985-05-01 00:00:00

  • The Role of TLR4 in Chemotherapy-Driven Metastasis.

    abstract::Tumor resistance to cytotoxic drugs is one of the main obstacles to successful cancer therapy. Emerging evidence suggests that chemoresistance is promoted by substances released from dead and damaged cells that activate the host repair program orchestrated by Toll-like receptor-4 (TLR4). TLR4 is often overexpressed in...

    journal_title:Cancer research

    pub_type: 杂志文章,评审

    doi:10.1158/0008-5472.CAN-14-3525

    authors: Ran S

    更新日期:2015-06-15 00:00:00

  • Prolonged chronic inflammation progresses to dysplasia in a novel rat model of colitis-associated colon cancer.

    abstract::Inflammatory bowel disease (IBD) is a gastrointestinal disorder of unknown etiology or cure. One complication of IBD is an increased risk for development of colon cancer. The aims of this study were to use a previously established rat model of colitis to develop a new model of colitis-associated colon cancer and ascer...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-1418

    authors: Santiago C,Pagán B,Isidro AA,Appleyard CB

    更新日期:2007-11-15 00:00:00

  • Ganglioside GD1alpha functions in the adhesion of metastatic tumor cells to endothelial cells of the target tissue.

    abstract::We studied the role of glycosphingolipids expressed on the cell surfaces of a metastatic tumor cell line. Glycosphingolipid compositions of the low-metastatic murine lymphosarcoma cell line RAW117-P and its sub-line, RAW117-H10, which shows higher metastatic potential for the liver than P cells, were compared. Both ty...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Taki T,Ishikawa D,Ogura M,Nakajima M,Handa S

    更新日期:1997-05-15 00:00:00

  • Inhibition of mouse alpha/beta-interferon of the multiplication of alpha/beta-interferon-resistant Friend erythroleukemia cells cocultured with mouse hepatocytes.

    abstract::Administration of alpha/beta-interferon (IFN) exerts a marked antitumor effect in DBA/2 mice given injections i.v. of large numbers of IFN-alpha/beta-resistant erythroleukemia cells (FLC). To investigate the possible mechanisms of FLC tumor inhibition in the liver of interferon-treated mice, we developed an in vitro m...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Yasui H,Proietti E,Vignaux F,Eid P,Gresser I

    更新日期:1990-06-15 00:00:00

  • Overexpression of ADAM9 in non-small cell lung cancer correlates with brain metastasis.

    abstract::The "a disintegrin and metalloprotease" (ADAM) family contributes to regulation of the cell-cell and cell-matrix interactions that are critical determinants of malignancy. To determine the relationship between metastasis and ADAM proteins, we compared the mRNA levels of ADAM9, -10, -12, -15, and -17 in sublines of an ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-03-3235

    authors: Shintani Y,Higashiyama S,Ohta M,Hirabayashi H,Yamamoto S,Yoshimasu T,Matsuda H,Matsuura N

    更新日期:2004-06-15 00:00:00

  • Induction of differentiation of the human histiocytic lymphoma cell line U-937 by retinoic acid and cyclic adenosine 3':5'-monophosphate-inducing agents.

    abstract::The monoblast-like human histiocytic lymphoma cell line, U-937, is induced to differentiate into monocyte-like cells by incubation with 0.1 to 1.0 microM retinoic acid (RA). These induced cells are phagocytic, reduce nitroblue tetrazolium, and show an increased hexose monophosphate shunt activity, consistent with mono...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Olsson IL,Breitman TR

    更新日期:1982-10-01 00:00:00

  • TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer.

    abstract::Although common in hematologic and mesenchymal malignancies, recurrent gene fusions have not been well characterized in epithelial carcinomas. Recently, using a novel bioinformatic approach, we identified recurrent gene fusions between TMPRSS2 and the ETS family members ERG or ETV1 in the majority of prostate cancers....

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-0168

    authors: Tomlins SA,Mehra R,Rhodes DR,Smith LR,Roulston D,Helgeson BE,Cao X,Wei JT,Rubin MA,Shah RB,Chinnaiyan AM

    更新日期:2006-04-01 00:00:00

  • Chemotherapy and chemosensitization of transgenic mice which express the human multidrug resistance gene in bone marrow: efficacy, potency, and toxicity.

    abstract::A common form of multidrug resistance in human cancer results from expression of the MDR1 gene which encodes a plasma membrane energy-dependent multidrug efflux pump. We have engineered transgenic mice which express this multidrug transporter in their bone marrow cells and demonstrated that peripheral WBC of these ani...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Mickisch GH,Licht T,Merlino GT,Gottesman MM,Pastan I

    更新日期:1991-10-01 00:00:00

  • Endogenous anti-HER2 antibodies block HER2 phosphorylation and signaling through extracellular signal-regulated kinase.

    abstract::Immunologic targeting of the oncoprotein HER2/neu with monoclonal antibodies is an important component of current therapeutic strategies for patients with locally and systemically advanced breast cancer. Engineered antibodies targeting HER2 may have agonist or antagonist effects on HER2, but little is known about whet...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Montgomery RB,Makary E,Schiffman K,Goodell V,Disis ML

    更新日期:2005-01-15 00:00:00

  • Integrity of SOS1/EPS8/ABI1 tri-complex determines ovarian cancer metastasis.

    abstract::Ovarian cancer is mainly confined in peritoneal cavity and its metastasis is often associated with the formation of malignant ascites. As lysophosphatidic acid (LPA) is present at high levels in ascites of ovarian cancer patients and potently stimulates cell migration, we reason that LPA-stimulated cell migration may ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-10-2394

    authors: Chen H,Wu X,Pan ZK,Huang S

    更新日期:2010-12-01 00:00:00

  • Cancer susceptibility of mice with a homozygous deletion in the COOH-terminal domain of the Brca2 gene.

    abstract::Inherited mutations of the human BRCA2 gene confer increased risks for developing breast, ovarian, and several other cancers. Unlike previously described Brca2 knockout mice that display predominantly embryonic lethal phenotypes, we developed mice with a homozygous germ-line deletion of Brca2 exon 27 that exhibit a mo...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: McAllister KA,Bennett LM,Houle CD,Ward T,Malphurs J,Collins NK,Cachafeiro C,Haseman J,Goulding EH,Bunch D,Eddy EM,Davis BJ,Wiseman RW

    更新日期:2002-02-15 00:00:00

  • Mechanism of cultured endothelial injury induced by lymphokine-activated killer cells.

    abstract::A new form of therapy of experimental tumors, utilizing lymphokine-activated killer (LAK) cells and high doses of interleukin 2, has recently been applied in the treatment of human neoplasms. Severe side effects, suggestive of a diffuse vascular injury of unknown etiology, have prevented a more widespread application ...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Kotasek D,Vercellotti GM,Ochoa AC,Bach FH,White JG,Jacob HS

    更新日期:1988-10-01 00:00:00

  • Immunohistopathology of lymph nodes in HTLV-III infected homosexuals with persistent adenopathy or AIDS.

    abstract::Lymph node biopsies from 43 male homosexuals with persistent generalized lymphadenopathy and from ten acquired immunodeficiency syndrome patients, all with serum antibodies to human T-cell leukemia virus III, were studied with regard to histopathology, immunohistology, and T-cell subsets in cell suspensions. All acqui...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Biberfeld P,Porwit-Ksiazek A,Böttiger B,Morfeldt-Månsson L,Biberfeld G

    更新日期:1985-09-01 00:00:00

  • Effects of prostacyclin on tumor cell-induced platelet aggregation.

    abstract::Prostacyclin has been evaluated for its ability to inhibit tumor cell-induced platelet aggregation (TCIPA) induced by several rodent tumor lines: B16a (melanoma); 3LL (carcinoma); 15091A (adenocarcinoma); and W256 (carcinosarcoma). Aggregation of human platelets by all four lines was inhibited by prostaglandin I2 (PGI...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Menter DG,Onoda JM,Taylor JD,Honn KV

    更新日期:1984-02-01 00:00:00

  • Effect of alpha-difluoromethylornithine on L-phenylalanine mustard-induced cytotoxicity and DNA interstrand cross-linking in a human cell line in vitro.

    abstract::We compared L-phenylalanine mustard (L-PAM)-induced cytotoxicity and DNA cross-linking with and without a 42-h preincubation with the ornithine decarboxylase inhibitor alpha-difluoromethylornithine (DFMO, 1 mM) in a human lymphoma cell line. The combination showed increased toxicity with a Do ratio of 1.6. L-PAM-induc...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Ducore JM,McNamara L

    更新日期:1986-03-01 00:00:00

  • Tumor angiogenesis activity in cells grown in tissue culture.

    abstract::Normal, viral transformed and tumor-derived cells grown in tissue culture and representing different species were tested for their ability to produce an extracellular tumor angiogenesis factor (TAF). TAF was assayed by measuring the host-mediated vascular response of the chorioallantoic membrane to TAF preparations. A...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Klagsbrun M,Knighton D,Folkman J

    更新日期:1976-01-01 00:00:00

  • Cancer stem cells contribute to cisplatin resistance in Brca1/p53-mediated mouse mammary tumors.

    abstract::The majority of BRCA1-associated breast cancers are basal cell-like, which is associated with a poor outcome. Using a spontaneous mouse mammary tumor model, we show that platinum compounds, which generate DNA breaks during the repair process, are more effective than doxorubicin in Brca1/p53-mutated tumors. At 0.5 mg/k...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-07-5480

    authors: Shafee N,Smith CR,Wei S,Kim Y,Mills GB,Hortobagyi GN,Stanbridge EJ,Lee EY

    更新日期:2008-05-01 00:00:00

  • Antisense oligonucleotides specific for transforming growth factor beta2 inhibit the growth of malignant mesothelioma both in vitro and in vivo.

    abstract::Transforming growth factor beta (TGF-beta) is a potent growth-regulatory and immunomodulatory cytokine that exerts a diverse range of effects on many types of cells. High levels of TGF-beta are produced by several human and mouse malignant mesothelioma (MM) cell lines, and it is known to act as a growth factor for the...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Marzo AL,Fitzpatrick DR,Robinson BW,Scott B

    更新日期:1997-08-01 00:00:00

  • Retinoid feeding, hormone inhibition, and/or immune stimulation and the genesis of carcinogen-induced rat mammary carcinomas.

    abstract::Female Sprague-Dawley rats were treated at 53 days of age with a single intubation of 7,12-dimethylbenzanthracene (DMBA). Three days after carcinogen treatment, the animals were treated with retinyl acetate (RA) (at 3 dietary levels), hormone inhibition (HI) [tamoxifen (1-rho-beta-dimethylaminoethoxyphenyl-trans-1,2-d...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Welsch CW,DeHoog JV

    更新日期:1983-02-01 00:00:00

  • Relationship between adenosine deaminase and a human thymus leukemia antigen isolated from MOLT 4 cells.

    abstract::The relationship between adenosine deaminase (ADA) and a human membrane thymus leukemia (HTL) antigen-detected by an antithymocyte serum was explored. A freeze-thaw extract of the T-cell-derived cell line, MOLT 4, was applied to an immunoabsorbant column of a rabbit antiserum to calf ADA. The bound MOLT 4 ADA was elut...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Dowell BL,Segars JH,Metzgar RS

    更新日期:1981-01-01 00:00:00

  • Presence of ras oncogene mutations and human papillomavirus DNA in human prostate carcinomas.

    abstract::The frequency of H-ras, K-ras, and N-ras mutations and the presence of high-risk human papillomavirus (HPV 16, 18, and 33) DNA were studied in 75 paraffin-embedded specimens obtained from 68 Japanese patients with a variety of prostate carcinomas by using polymerase chain reaction and DNA hybridization with sequence-s...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Anwar K,Nakakuki K,Shiraishi T,Naiki H,Yatani R,Inuzuka M

    更新日期:1992-11-01 00:00:00

  • Retinoic acid-induced expression of CD38 antigen in myeloid cells is mediated through retinoic acid receptor-alpha.

    abstract::CD38 is a leukocyte differentiation antigen that has been thought to be a phenotypic marker of different subpopulations of T- and B-lymphocytes. In myeloid cells, CD38 is expressed during early stages of differentiation. Virtually no information is available on regulation and functions of CD38. Recently we reported th...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:

    authors: Drach J,McQueen T,Engel H,Andreeff M,Robertson KA,Collins SJ,Malavasi F,Mehta K

    更新日期:1994-04-01 00:00:00

  • Hemizygous disruption of Cdc25A inhibits cellular transformation and mammary tumorigenesis in mice.

    abstract::CDC25A phosphatase activates multiple cyclin-dependent kinases (CDK) during cell cycle progression. Inactivation of CDC25A by ubiquitin-mediated degradation is a major mechanism of DNA damage-induced S-G(2) checkpoint. Although increased CDC25A expression has been reported in various human cancer tissues, it remains u...

    journal_title:Cancer research

    pub_type: 杂志文章

    doi:10.1158/0008-5472.CAN-06-4815

    authors: Ray D,Terao Y,Nimbalkar D,Hirai H,Osmundson EC,Zou X,Franks R,Christov K,Kiyokawa H

    更新日期:2007-07-15 00:00:00