Intrinsic Mitochondrial Membrane Potential and Associated Tumor Phenotype Are Independent of MUC1 Over-Expression
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{"title"=>"Intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of MUC1 over-expression", "type"=>"journal", "authors"=>[{"first_name"=>"Michele A.", "last_name"=>"Houston", "scopus_author_id"=>"7103236356"}, {"first_name"=>"Leonard H.", "last_name"=>"Augenlicht", "scopus_author_id"=>"7004774947"}, {"first_name"=>"Barbara G.", "last_name"=>"Heerdt", "scopus_author_id"=>"7003724738"}], "year"=>2011, "source"=>"PLoS ONE", "identifiers"=>{"pui"=>"362619297", "pmid"=>"21966455", "doi"=>"10.1371/journal.pone.0025207", "scopus"=>"2-s2.0-80053115993", "isbn"=>"1932-6203 (Electronic)\r1932-6203 (Linking)", "issn"=>"19326203", "sgr"=>"80053115993"}, "id"=>"415d25c5-26f5-38d5-b6d6-37deb76aad76", "abstract"=>"We have established previously that minor subpopulations of cells with stable differences in their intrinsic mitochondrial membrane potential (Δψm) exist within populations of mammary and colonic carcinoma cells and that these differences in Δψm are linked to tumorigenic phenotypes consistent with increased probability of participating in tumor progression. However, the mechanism(s) involved in generating and maintaining stable differences in intrinsic Δψm and how they are linked to phenotype are unclear. Because the mucin 1 (MUC1) oncoprotein is over-expressed in many cancers, with the cytoplasmic C-terminal fragment (MUC1 C-ter) and its integration into the outer mitochondrial membrane linked to tumorigenic phenotypes similar to those of cells with elevated intrinsic Δψm, we investigated whether endogenous differences in MUC1 levels were linked to stable differences in intrinsic Δψm and/or to the tumor phenotypes associated with the intrinsic Δψm. We report that levels of MUC1 are significantly higher in subpopulations of cells with elevated intrinsic Δψm derived from both mammary and colonic carcinoma cell lines. However, using siRNA we found that down-regulation of MUC1 failed to significantly affect either the intrinsic Δψm or the tumor phenotypes associated with increased intrinsic Δψm. Moreover, whereas pharmacologically mediated disruption of the Δψm was accompanied by attenuation of tumor phenotype, it had no impact on MUC1 levels. Therefore, while MUC1 over-expression is associated with subpopulations of cells with elevated intrinsic Δψm, it is not directly linked to the generation or maintenance of stable alterations in intrinsic Δψm, or to intrinsic Δψm associated tumor phenotypes. Since the Δψm is the focus of chemotherapeutic strategies, these data have important clinical implications in regard to effectively targeting those cells within a tumor cell population that exhibit stable elevations in intrinsic Δψm and are most likely to contribute to tumor progression.", "link"=>"http://www.mendeley.com/research/intrinsic-mitochondrial-membrane-potential-associated-tumor-phenotype-independent-muc1-overexpressio", "reader_count"=>7, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>2, "Medicine and Dentistry"=>2, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/731496"], "description"=>"<p><b>A:</b> Steady state mRNA levels of MUC1 were determined by qRT-PCR, normalized to GAPDH, in the parental population of SW620 cells and in subcloned cell lines derived from SW620 cells that have a range stable intrinsic Δψm. (*; <i>P</i><0.001 vs. the population of SW620 cells.) <b>B:</b> Immunoblots of mt and PMF from the SW620 colonic carcinoma cell population and from subcloned lines derived from SW620 cells with intrinsic Δψm higher (↑Δψm), lower (↓Δψm) and comparable (≈Δψm) to that of the population were probed with anti-MUC1 C-ter and anti-VDAC and chemiluminescence signals quantified and expressed as a function of the intrinsic Δψm, determined by JC-1 staining, using linear regression analyses. MUC1 C-ter, but not VDAC, levels in both mt enriched and PMF are significantly associated with the intrinsic Δψm (<i>P</i> = 0.0053 and 0.0032, respectively).</p>", "links"=>[], "tags"=>["muc1", "levels", "differences", "intrinsic", "subcloned", "lines", "derived", "sw620", "colonic", "carcinoma"], "article_id"=>401840, "categories"=>["Cancer", "Cell Biology", "Genetics", "Mathematics"], "users"=>["Michele A. Houston", "Leonard H. Augenlicht", "Barbara G. Heerdt"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025207.g001", "stats"=>{"downloads"=>2, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Constitutive_MUC1_levels_are_associated_with_stable_differences_in_intrinsic_916_968_m_of_subcloned_cell_lines_derived_from_SW620_colonic_carcinoma_cell_population_/401840", "title"=>"Constitutive MUC1 levels are associated with stable differences in intrinsic Δψm of subcloned cell lines derived from SW620 colonic carcinoma cell population.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 14:24:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/731663"], "description"=>"<p>Mt-associated MUC1 C-ter levels were determined by immunoblotting in mt enriched fractions isolated from the population of SW480 (<b>A</b>) and MCF7 (<b>B</b>) cells and from subclones derived from these cell populations that have stable intrinsic Δψm ranging from significantly lower to significantly higher than that of the population. MUC1 C-ter levels are expressed as a function of the relative intrinsic Δψm by linear regression analyses.</p>", "links"=>[], "tags"=>["mt-associated", "muc1", "c-ter", "levels", "differences", "intrinsic", "subcloned", "lines", "derived", "sw480", "colonic", "mcf7", "mammary", "carcinoma"], "article_id"=>402003, "categories"=>["Cancer", "Cell Biology", "Genetics", "Mathematics"], "users"=>["Michele A. Houston", "Leonard H. Augenlicht", "Barbara G. Heerdt"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025207.g002", "stats"=>{"downloads"=>0, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Constitutive_mt_associated_MUC1_C_ter_levels_are_associated_with_stable_differences_in_intrinsic_916_968_m_of_subcloned_cell_lines_derived_from_SW480_colonic_and_MCF7_mammary_carcinoma_cell_populations_/402003", "title"=>"Constitutive mt-associated MUC1 C-ter levels are associated with stable differences in intrinsic Δψm of subcloned cell lines derived from SW480 colonic and MCF7 mammary carcinoma cell populations.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 14:25:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/731759"], "description"=>"<p>Subcloned cell lines with intrinsic Δψm higher (↑Δψm), lower (↓Δψm) and comparable (≈Δψm) to that of the population, and the SW620 parental population, were mock transfected, or transfected with NT- or MUC1-siRNA. Twenty-four, 48 and 72 hours later levels of MUC1 mRNA were determined by qRT-PCR, normalized to GAPDH. The level of MUC1 mRNA in the siRNA-MUC1 transfected cell line with ↑Δψm did not differ significantly from that of mock transfected SW620 cell population 48 and 72 hours after transfection (<i>P</i>>0.05).</p>", "links"=>[], "tags"=>["sirna-mediates", "muc1", "subcloned", "lines", "intrinsic"], "article_id"=>402115, "categories"=>["Cancer", "Cell Biology", "Genetics", "Mathematics"], "users"=>["Michele A. Houston", "Leonard H. Augenlicht", "Barbara G. Heerdt"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025207.g003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_MUC1_siRNA_mediates_down_regulation_of_MUC1_expression_in_subcloned_cell_lines_with_different_intrinsic_916_968_m_/402115", "title"=>"MUC1 siRNA-mediates down regulation of MUC1 expression in subcloned cell lines with different intrinsic Δψm.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 14:26:10"}
  • {"files"=>["https://ndownloader.figshare.com/files/731896"], "description"=>"<p>Cells were mock, MUC1- or NT-siRNA transfected. Twenty-four, 48 and 72 hours later, levels of cell surface MUC1 N-ter were determined by flow cytometry (<b>A</b>); levels of mt-associated MUC1 C-ter determined by quantitative immunoblotting (<b>B</b>) and the Δψm was determined by JC-1 staining and flow cytometry.</p>", "links"=>[], "tags"=>["muc1", "n-ter", "mt-associated", "c-ter", "levels"], "article_id"=>402244, "categories"=>["Cancer", "Cell Biology", "Genetics", "Mathematics"], "users"=>["Michele A. Houston", "Leonard H. Augenlicht", "Barbara G. Heerdt"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025207.g004", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_siRNA_mediated_down_regulation_of_MUC1_N_ter_and_mt_associated_C_ter_levels_does_not_affect_the_916_968_m_/402244", "title"=>"siRNA-mediated down regulation of MUC1 N-ter and mt-associated C-ter levels does not affect the Δψm.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 14:26:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/732173"], "description"=>"<p>Cells were mock, MUC1- or NT-siRNA transfected and 48 hours later VEGF secretion levels were determined in harvested conditioned tissue culture medium.</p>", "links"=>[], "tags"=>["mediated", "down-regulation", "muc1", "intrinsic", "constitutive", "hypoxia-independent", "vegf"], "article_id"=>402523, "categories"=>["Cancer", "Cell Biology", "Genetics", "Mathematics"], "users"=>["Michele A. Houston", "Leonard H. Augenlicht", "Barbara G. Heerdt"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025207.g006", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_siRNA_mediated_down_regulation_of_MUC1_does_not_affect_intrinsic_916_968_m_linked_constitutive_hypoxia_independent_VEGF_secretion_/402523", "title"=>"siRNA mediated down-regulation of MUC1 does not affect intrinsic Δψm-linked constitutive hypoxia-independent VEGF secretion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 14:28:21"}
  • {"files"=>["https://ndownloader.figshare.com/files/732079"], "description"=>"<p>Cells were mock, MUC1- or NT-siRNA transfected and 48 hours later and then exposed to 5 mM NaB for 24 hours. Percentage of apoptotic cells was determined by PI staining and flow cytometry.</p>", "links"=>[], "tags"=>["mediated", "down-regulation", "muc1", "intrinsic", "butyrate", "induced"], "article_id"=>402429, "categories"=>["Cancer", "Cell Biology", "Genetics", "Mathematics"], "users"=>["Michele A. Houston", "Leonard H. Augenlicht", "Barbara G. Heerdt"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025207.g005", "stats"=>{"downloads"=>1, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_siRNA_mediated_down_regulation_of_MUC1_does_not_affect_intrinsic_916_968_m_linked_sensitivity_to_butyrate_NaB_induced_apoptosis_/402429", "title"=>"siRNA mediated down-regulation of MUC1 does not affect intrinsic Δψm-linked sensitivity to butyrate (NaB) induced apoptosis.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 14:27:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/732248"], "description"=>"<p>Cells were exposed to 5 µM valinomycin overnight and then stained with JC-1 or FITC-conjugated anti-human MUC1 (CD227) and analyzed by flow cytometry for quantitation of Δψm and cell surface MUC1 N-ter, respectively. Levels of VEGF<sub>165</sub> were quantified in conditioned tissue culture medium harvested from untreated and valinomycin treated cells (#; <i>P</i><0.05 valinomycin vs. untreated) (<b>A</b>). Levels of MUC1 C-ter were determined in mitochondrial enriched fractions by immunoblotting (<b>B</b>).</p>", "links"=>[], "tags"=>["mediated", "disruption", "muc1", "levels", "attenuates", "intrinsic", "constitutive", "hypoxia-independent", "vegf"], "article_id"=>402591, "categories"=>["Cancer", "Cell Biology", "Genetics", "Mathematics"], "users"=>["Michele A. Houston", "Leonard H. Augenlicht", "Barbara G. Heerdt"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0025207.g007", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Pharmacologically_mediated_disruption_of_the_916_968_m_does_not_affect_MUC1_levels_but_attenuates_intrinsic_916_968_m_linked_constitutive_hypoxia_independent_VEGF_secretion_/402591", "title"=>"Pharmacologically mediated disruption of the Δψm does not affect MUC1 levels but attenuates intrinsic Δψm-linked constitutive hypoxia-independent VEGF secretion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 14:28:43"}

PMC Usage Stats | Further Information

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Relative Metric

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