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Moiola, C.P.; Luca, P.D.; Zalazar, F.; Cotignola, J.; Rodríguez-Seguí, S.A.; Gardner, K.; Meiss, R.; Vallecorsa, P.; Pignataro, O.; Mazza, O.; Vazquez, E.S.; De Siervi, A. "Prostate tumor growth is impaired by CtBP1 depletion in high-fat diet-fed mice" (2014) Clinical Cancer Research. 20(15):4086-4095
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Abstract:

Purpose: Clinical and epidemiologic data suggest that obesity is associated with more aggressive forms of prostate cancer, poor prognosis, and increased mortality. C-terminal-binding protein 1 (CtBP1) is a transcription repressor of tumor suppressor genes and is activated by NADH binding. High calorie intake decreases intracellular NAD+/NADH ratio. The aim of this work was to assess the effect of high-fat diet (HFD) and CtBP1 expression modulation over prostate xenograft growth. Experimental Design: We developed a metabolic syndrome-like disease in vivo model by feeding male nude mice with HFD during 16 weeks. Control diet (CD)-fed animals were maintained at the same conditions. Mice were inoculated with PC3 cells stable transfected with shCtBP1 or control plasmids. Genome-wide expression profiles and Gene Set Enrichment Analysis (GSEA) were performed from PC3. shCtBP1 versus PC3.pGIPZ HFD-fed mice tumors. Results: No significant differences were observed in tumor growth on CD-fed mice; however, we found that only 60% of HFD-fed mice inoculated with CtBP1-depleted cells developed a tumor. Moreover these tumors were significantly smaller than those generated by PC3.pGIPZ control xenografts. We found 823 genes differentially expressed in shCtBP1 tumors from HFD-fed mice. GSEA from expression dataset showed that most of these genes correspond to cell adhesion, metabolic process, and cell cycle. Conclusions: Metabolic syndrome-like diseases and CtBP1 expression cooperate to induce prostate tumor growth. Hence, targeting of CtBP1 expression might be considered for prostate cancer management and therapy in the subset of patients with metabolic syndromes. © 2014 American Association for Cancer Research.

Registro:

Documento: Artículo
Título:Prostate tumor growth is impaired by CtBP1 depletion in high-fat diet-fed mice
Autor:Moiola, C.P.; Luca, P.D.; Zalazar, F.; Cotignola, J.; Rodríguez-Seguí, S.A.; Gardner, K.; Meiss, R.; Vallecorsa, P.; Pignataro, O.; Mazza, O.; Vazquez, E.S.; De Siervi, A.
Filiación:Laboratorio de Oncología Molecular y Nuevos Blancos Terapeuticos, IBYME-CONICET, Vuelta de Obligado 2490, Buenos Aires, C1428ADN, Argentina
Laboratorio de Inflamacion y Cancer, Departamento de Química Biologica, Facultad de Ciencias Exactas y Naturales (FCEN), Buenos Aires, Argentina
Laboratorio de Endocrinología Molecular y Transduccion de Senales, Departamento de Química Biologica, Facultad de Ciencias Exactas y Naturales (FCEN), Buenos Aires, Argentina
Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales (FCEN), Universidad de Buenos Aires (UBA), Buenos Aires, Argentina
Departamento de Patología, Instituto de Estudios Oncologicos, Academia Nacional de Medicina, Buenos Aires, Argentina
Hospital de Clínicas Jose de San Martín, Buenos Aires, Argentina
Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
Palabras clave:carboxy terminal binding protein 1; tumor suppressor protein; unclassified drug; alcohol dehydrogenase; C-terminal binding protein; DNA binding protein; messenger RNA; sex hormone; small interfering RNA; tumor marker; animal cell; animal experiment; animal model; animal tissue; article; cancer inhibition; cell adhesion; cell cycle; controlled study; gene expression; gene identification; genetic analysis; in vitro study; in vivo study; lipid diet; male; metabolism; mouse; nonhuman; priority journal; prostate cancer; protein depletion; protein function; adverse effects; animal; antagonists and inhibitors; apoptosis; cell proliferation; cell transformation; chromatin immunoprecipitation; DNA microarray; drug effects; drug screening; enzyme immunoassay; gene expression profiling; genetics; human; lipid diet; metabolic syndrome X; nude mouse; obesity; pathology; Prostatic Neoplasms; real time polymerase chain reaction; reverse transcription polymerase chain reaction; tumor cell culture; Western blotting; Alcohol Oxidoreductases; Animals; Apoptosis; Blotting, Western; Cell Adhesion; Cell Proliferation; Cell Transformation, Neoplastic; Chromatin Immunoprecipitation; Diet, High-Fat; DNA-Binding Proteins; Gene Expression Profiling; Gonadal Steroid Hormones; Humans; Immunoenzyme Techniques; Male; Metabolic Syndrome X; Mice; Mice, Nude; Obesity; Oligonucleotide Array Sequence Analysis; Prostatic Neoplasms; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering; Tumor Cells, Cultured; Tumor Markers, Biological; Xenograft Model Antitumor Assays
Año:2014
Volumen:20
Número:15
Página de inicio:4086
Página de fin:4095
DOI: http://dx.doi.org/10.1158/1078-0432.CCR-14-0322
Título revista:Clinical Cancer Research
Título revista abreviado:Clin. Cancer Res.
ISSN:10780432
CODEN:CCREF
CAS:alcohol dehydrogenase, 9031-72-5; Alcohol Oxidoreductases; C-terminal binding protein; DNA-Binding Proteins; Gonadal Steroid Hormones; RNA, Messenger; RNA, Small Interfering; Tumor Markers, Biological
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_10780432_v20_n15_p4086_Moiola

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Citas:

---------- APA ----------
Moiola, C.P., Luca, P.D., Zalazar, F., Cotignola, J., Rodríguez-Seguí, S.A., Gardner, K., Meiss, R.,..., De Siervi, A. (2014) . Prostate tumor growth is impaired by CtBP1 depletion in high-fat diet-fed mice. Clinical Cancer Research, 20(15), 4086-4095.
http://dx.doi.org/10.1158/1078-0432.CCR-14-0322
---------- CHICAGO ----------
Moiola, C.P., Luca, P.D., Zalazar, F., Cotignola, J., Rodríguez-Seguí, S.A., Gardner, K., et al. "Prostate tumor growth is impaired by CtBP1 depletion in high-fat diet-fed mice" . Clinical Cancer Research 20, no. 15 (2014) : 4086-4095.
http://dx.doi.org/10.1158/1078-0432.CCR-14-0322
---------- MLA ----------
Moiola, C.P., Luca, P.D., Zalazar, F., Cotignola, J., Rodríguez-Seguí, S.A., Gardner, K., et al. "Prostate tumor growth is impaired by CtBP1 depletion in high-fat diet-fed mice" . Clinical Cancer Research, vol. 20, no. 15, 2014, pp. 4086-4095.
http://dx.doi.org/10.1158/1078-0432.CCR-14-0322
---------- VANCOUVER ----------
Moiola, C.P., Luca, P.D., Zalazar, F., Cotignola, J., Rodríguez-Seguí, S.A., Gardner, K., et al. Prostate tumor growth is impaired by CtBP1 depletion in high-fat diet-fed mice. Clin. Cancer Res. 2014;20(15):4086-4095.
http://dx.doi.org/10.1158/1078-0432.CCR-14-0322