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Expression data from a model of human mammary stem cells at different stages of transformation, sorted or not on the basis of their CD10 expression

ABSTRACT: This study was designed to follow the transcriptome changes during BMP2 mediated transformation of the MCF10A human mammary stem cell model. We found that long-term BMP2/IL6 exposure of MCF10A cells, human immortalized but non-transformed mammary stem cells and progenitors, led to their luminal transformation. MC26 cells correspond to MCF10A cells transformed by BMP2/IL6 long-term exposure and contrarily to their parental cells, are able to engraft in immunodeficient mice and form colonies in soft-agar. M1B26 cells were obtained after BMP2/IL-6 long-term treatment of MCF10A cells sorted for high BMPR1B expression and subsequent isolation and expansion of 3 soft-agar colonies. M1B26 have an increased ability to engraft in mice and form colonies in soft-agar when compared to MC26 cells. As a non-transformed control, MCF10A-CT cells were kept in culture without BMP2/IL6 for the same length of time than MC26 cells. MCF10A-CT, MC26 and M1B26 cells are thus a model allowing to follow the molecular events associated with the initiation of a luminal transformation in mammary stem cells. Expression of the CD10 membrane endopeptidase has been associated with cancer although it can be a marker of both good or poor prognosis depending on the stage of the cancer and on the tissue of origin. In addition, we showed that CD10 was a marker of stem cell containing populations in healthy mammary tissue and that CD10 enzymatic activity was involved in the maintenance of cells immature properties. Having recently shown that CD10 expression was increasing during BMP2 mediated transformation and that CD10 expressing cells were more transformed but that CD10 was not required for transformation, we set out to determine the gene signature associated with CD10 expression.

ORGANISM(S): Homo sapiens

PROVIDER: GSE123053 | GEO | 2023/09/01

REPOSITORIES: GEO

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Project description:Pentavalent vanadium compounds induce intracellular changes in vitro that are consistent with those of other carcinogenic substances, including alteration of transcription factor levels, promotion of oxidative stress, inflammation, DNA damage, stimulation of mitogenic signals, and suppression of apoptosis. While there is no clear evidence that vanadium compounds cause cancer in humans, vanadium pentoxide causes lung cancer in rodents after long-term inhalation exposures and in turn IARC has categorized it as a group 2B possible human carcinogen. The goal of this study was to investigate the carcinogenicity of NaVO3 in the human immortalized bronchial epithelial cell line, Beas-2B. Cells were treated with 10 ÂµM NaVO3 for 5 weeks, with or without recovery time, followed by gene expression microarray analysis. In a separate experiment, cells were exposed to 1-10 ÂµM NaVO3 for 4 weeks and then grown in soft agar to test for anchorage-independent growth. A dose-dependent increase in the number of colonies was observed. NaVO3-transformed clones could repair a wound faster than controls during the scratch test. In a gene expression microarray analysis of soft agar clones there were 2010 differentially expressed genes (DEG) (adjusted p-value â¤ 0.05) in NaVO3-transformed clones relative to control clones. DEG from this experiment were compared with the DEG of 5 week NaVO3 exposure with or without recovery, all with adjusted p-values <0.05, and 469 genes were altered in the same direction for transformed clones, 5 week NaVO3-treated cells, and the recovered cells; a subset of these changes were validated by QRT-PCR. The data from this study imply that chronic exposure to NaVO3 causes changes that are consistent with cellular transformation including anchorage- independent growth, enhanced migration ability, and gene expression changes that were epigenetically inherited through cell division. Beas-2B cells were chronically exposed to sodium metavanadate in growth media for 4 weeks. Then exposed cells and unexposed control cells were grown in soft agar for 3 weeks in the absence of vanadate. Transformed colonies (arising from vanadate-exposed cells) and control colonies (spontaneously grew from unexposed cells) were extracted from soft agar and expanded in the absence of vanadate, then processed for gene expression analysis on Affymetrix GeneChip Human Exon 1.0 ST array. 5 transformed clones, 3 control clones, 1 parental Beas-2B cell sample, and acute 24 hour vanadate exposed cell samples were analyzed.

Project description:Pentavalent vanadium compounds induce intracellular changes in vitro that are consistent with those of other carcinogenic substances, including alteration of transcription factor levels, promotion of oxidative stress, inflammation, DNA damage, stimulation of mitogenic signals, and suppression of apoptosis. While there is no clear evidence that vanadium compounds cause cancer in humans, vanadium pentoxide causes lung cancer in rodents after long-term inhalation exposures and in turn IARC has categorized it as a group 2B possible human carcinogen. The goal of this study was to investigate the carcinogenicity of NaVO3 in the human immortalized bronchial epithelial cell line, Beas-2B. Cells were treated with 10 M-BM-5M NaVO3 for 5 weeks, with or without recovery time, followed by gene expression microarray analysis. In a separate experiment, cells were exposed to 1-10 M-BM-5M NaVO3 for 4 weeks and then grown in soft agar to test for anchorage-independent growth. A dose-dependent increase in the number of colonies was observed. NaVO3-transformed clones could repair a wound faster than controls during the scratch test. In a gene expression microarray analysis of soft agar clones there were 2010 differentially expressed genes (DEG) (adjusted p-value M-bM-^IM-$ 0.05) in NaVO3-transformed clones relative to control clones. DEG from this experiment were compared with the DEG of 5 week NaVO3 exposure with or without recovery, all with adjusted p-values <0.05, and 469 genes were altered in the same direction for transformed clones, 5 week NaVO3-treated cells, and the recovered cells; a subset of these changes were validated by QRT-PCR. The data from this study imply that chronic exposure to NaVO3 causes changes that are consistent with cellular transformation including anchorage- independent growth, enhanced migration ability, and gene expression changes that were epigenetically inherited through cell division. Beas-2B cells were chronically exposed to sodium metavanadate in growth media for 4 weeks. Then, one set of exposed cells and unexposed control cells were grown in soft agar for 3 weeks in the absence of vanadate. Transformed colonies (arising from vanadate-exposed cells) and control colonies (spontaneously grew from unexposed cells) were extracted from soft agar and expanded in the absence of vanadate, then processed for gene expression analysis . A second set of exposed cells continued treatment for a total of 5 weeks exposure. A third set of cells recovered for 1 week after the 4 week long exposure. The gene expression of 5 transformed clones, 3 control clones, 2 5 week exposures, 2 recovery, and 2 unexposed control cells, and 1 parental Beas-2B cell samples were analyzed (15 total samples) with an Affymetrix GeneChip Human Exon 1.0 ST array.

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Expression data from a model of human mammary stem cells at different stages of transformation, sorted or not on the basis of their CD10 expression

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