Intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of MUC1 over-expression.

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 i...

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Main Authors: Michele A Houston, Leonard H Augenlicht, Barbara G Heerdt
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3179472?pdf=render
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spelling doaj-de33c13d87364fdfb6e06aca65ea589c2020-11-25T02:22:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0169e2520710.1371/journal.pone.0025207Intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of MUC1 over-expression.Michele A HoustonLeonard H AugenlichtBarbara G HeerdtWe 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.http://europepmc.org/articles/PMC3179472?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Michele A Houston
Leonard H Augenlicht
Barbara G Heerdt
spellingShingle Michele A Houston
Leonard H Augenlicht
Barbara G Heerdt
Intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of MUC1 over-expression.
PLoS ONE
author_facet Michele A Houston
Leonard H Augenlicht
Barbara G Heerdt
author_sort Michele A Houston
title Intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of MUC1 over-expression.
title_short Intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of MUC1 over-expression.
title_full Intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of MUC1 over-expression.
title_fullStr Intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of MUC1 over-expression.
title_full_unstemmed Intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of MUC1 over-expression.
title_sort intrinsic mitochondrial membrane potential and associated tumor phenotype are independent of muc1 over-expression.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2011-01-01
description 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.
url http://europepmc.org/articles/PMC3179472?pdf=render
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