Growth and differentiation of progenitor/stem cells derived from the human mammary gland

Clayton, Helen; Titley, Ian; Vivanco, María dM

doi:10.1016/j.yexcr.2004.03.029

Cited by 158 publications

(169 citation statements)

References 59 publications

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“…Investigators first determined that stem cells from rhesus monkey bone marrow, mouse skeletal muscle and murine embryonic stem cells, which constitute the 'side population' of effluxing cells, expressed ABCG2 (Zhou et al, 2001). In addition, the expression of ABCG2 has been linked to prostate stem cells and mammary gland stem cells (Clayton et al, 2004;Huss et al, 2005). ABCG2 may serve as the primary line of defence against the cytotoxic effects of drug in our single-step-selected clones, as it does in stem cells.…”

Section: Discussionmentioning

confidence: 99%

Single-step doxorubicin-selected cancer cells overexpress the ABCG2 drug transporter through epigenetic changes

Calcagno

Fostel²,

et al. 2008

Br J Cancer

111

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Understanding the mechanisms of multidrug resistance (MDR) could improve clinical drug efficacy. Multidrug resistance is associated with ATP binding cassette (ABC) transporters, but the factors that regulate their expression at clinically relevant drug concentrations are poorly understood. We report that a single-step selection with low doses of anti-cancer agents, similar to concentrations reported in vivo, induces MDR that is mediated exclusively by ABCG2. We selected breast, ovarian and colon cancer cells (MCF-7, IGROV-1 and S-1) after exposure to 14 or 21 nM doxorubicin for only 10 days. We found that these cells overexpress ABCG2 at the mRNA and protein levels. RNA interference analysis confirmed that ABCG2 confers drug resistance. Furthermore, ABCG2 upregulation was facilitated by histone hyperacetylation due to weaker histone deacetylase 1-promoter association, indicating that these epigenetic changes elicit changes in ABCG2 gene expression. These studies indicate that the MDR phenotype arises following low-dose, single-step exposure to doxorubicin, and further suggest that ABCG2 may mediate early stages of MDR development. This is the first report to our knowledge of single-step, low-dose selection leading to overexpression of ABCG2 by epigenetic changes in multiple cancer cell lines.

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Section: Discussionmentioning

confidence: 99%

Single-step doxorubicin-selected cancer cells overexpress the ABCG2 drug transporter through epigenetic changes

Calcagno

Fostel²,

et al. 2008

Br J Cancer

111

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“…Neural stem cells (NSCs) have the ability to self-renew and to differentiate into distinct cell types of the central nervous system [57][58][59][60][62][63][64][65] The identification of these putative progenitors has largely been based on cell culture assays with more limited information available on their ability to generate a functional mammary ductal-lobular unit. Among others mammosphere cultures have been used to enrich for putative mammary stem cells based on their ability to proliferate in suspension.…”

Section: Epigenetic Programs Of Adult Stem Cellsmentioning

confidence: 99%

Epigenetic patterns of embryonic and adult stem cells

Bloushtain-Qimron

Yao²,

Shipitsin

et al. 2009

Cell Cycle

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“…Recently, however, it has become clear that another ABC transporter, Breast Cancer Resistance Protein (BCRP/ABCG2), is mainly responsible for the SP phenotype, at least in bone marrow [2][3][4][5][6]. Based on the initial findings in the hematopoietic compartment, SP cells have now been identified in many other tissues including the mammary gland [7][8][9], skeletal muscle, pancreas, lung, retina, liver, testis, heart, and epidermis [10][11][12][13][14][15][16][17]. In addition to normal tissues, it has further been demonstrated that cancer cell lines and primary tumor cells contain an SP [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Contribution of the ABC Transporters Bcrp1 and Mdr1a/1b to the Side Population Phenotype in Mammary Gland and Bone Marrow of Mice

et al. 2005

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The ability of cells to export Hoechst 33342 can be used to identify a subpopulation of cells (side population [SP]) with characteristics of stem cells in many tissues. The ATP-binding cassette transporters Bcrp1 (Abcg2) and Mdr1a/1b (Abcb1a/1b) have been implicated as being responsible for this phenotype. To further explore the involvement of these transporters in the SP phenotype, we have generated Bcrp1/ Mdr1a/1b triple knockout mice and studied the effect of their absence on the SP in bone marrow and mammary gland.Whereas in bone marrow Bcrp1 was almost exclusively responsible for the SP, both transporters contributed to the SP phenotype in the mammary gland, where their combined absence resulted in a nearly complete loss of SP. Interestingly, bone marrow of Mdr1a/1b −/− mice frequently displayed an elevated SP, which was reversible by the Bcrp1 inhibitor Ko143, suggesting that Bcrp1 can compensate for the loss of Mdr1a/1b in bone marrow. Stem Cells 2005;23:1059-1065

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Growth and differentiation of progenitor/stem cells derived from the human mammary gland

Cited by 158 publications

References 59 publications

Single-step doxorubicin-selected cancer cells overexpress the ABCG2 drug transporter through epigenetic changes

Single-step doxorubicin-selected cancer cells overexpress the ABCG2 drug transporter through epigenetic changes

Epigenetic patterns of embryonic and adult stem cells

Contribution of the ABC Transporters Bcrp1 and Mdr1a/1b to the Side Population Phenotype in Mammary Gland and Bone Marrow of Mice

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