Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer

Molyneux, Gemma; Regan, Joseph L.; Smalley, Matthew J.

doi:10.1007/s00018-007-7391-5

Cited by 48 publications

(23 citation statements)

References 103 publications

(113 reference statements)

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“…Particularly, BRCA1 -mutated basal-like breast cancers are believed to arise from the luminal progenitors [7, 8, 27, 28]. Here, we have identified an additional reliable antigen, CD338/ABCG2, that can be used to refine the sorting of the luminal progenitor subpopulations of BRCA1 -mutated breast cancer cells.…”

Section: Resultsmentioning

confidence: 99%

“…BRCA1 -mutated basal-like breast cancers are believed to arise from a developmental stage of the mammary epithelial cell, which is different from the primitive stem cell, named the luminal progenitors [7, 8, 40, 41]. It is noteworthy that CD338 + cells in mammosphere-derived HCC1937 cells are the only cell subpopulation that maintained the expression of CD326/EpCAM and CD49f/ α6-integrin, a combination of antigens previously assigned to luminal progenitors [7].…”

Section: Discussionmentioning

confidence: 99%

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ABCG2, a novel antigen to sort luminal progenitors of BRCA1- breast cancer cells

et al. 2014

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IntroductionTumor-initiating cells (TICs), aka “cancer stem cells”, are believed to fuel tumors and to sustain therapy resistance and systemic metastasis. Breast cancer is the first human carcinoma in which a subpopulation of cells displaying a specific CD44+/CD24-/low/ESA+ antigenic phenotype was found to have TIC properties. However, CD44+/CD24-/low/ESA+ is not a universal marker phenotype of TICs in all breast cancer subtypes. The aim of this study was to identify novel antigens with which to isolate the TIC population of the basal-A/basal-like breast cancer cell lines.MethodsWe used polychromatic flow-cytometry to characterize the cell surface of several breast cancer cell lines that may represent different tumor molecular subtypes. We next used fluorescence-activated cell sorting to isolate the cell subpopulations of interest from the cell lines. Finally, we explored the stem-like and tumorigenic properties of the sorted cell subpopulations using complementary in vitro and in vivo approaches: mammosphere formation assays, soft-agar colony assays, and tumorigenic assays in NOD/SCID mice.ResultsThe CD44+/CD24+ subpopulation of the BRCA1-mutated basal-A/basal-like cell line HCC1937 is enriched in several stemness markers, including the ABCG2 transporter (i.e., the CD338 antigen). Consistently, CD338-expressing cells were also enriched in CD24 expression, suggesting that coexpression of these two antigenic markers may segregate TICs in this cell line. In support of ABCG2 expression in TICs, culturing of HCC1937 cells in ultra-low adherent conditions to enrich them in precursor/stem-cells resulted in an increase in CD338-expressing cells. Furthermore, CD338-expressing cells, unlike their CD338-negative counterparts, displayed stemness and transformation potential, as assessed in mammosphere and colony formation assays. Lastly, CD338-expressing cells cultured in ultra-low adherent conditions maintained the expression of CD326/EpCAM and CD49f/α6-integrin, which is a combination of antigens previously assigned to luminal progenitors.ConclusionCollectively, our data suggest that CD338 expression is specific to the tumor-initiating luminal progenitor subpopulation of BRCA1-mutated cells and is a novel antigen with which to sort this subpopulation.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-213) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

ABCG2, a novel antigen to sort luminal progenitors of BRCA1- breast cancer cells

et al. 2014

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“…Manifestation of the cancer stem cell hypothesis, which identifies normal mammary stem cells (MaSC) and their immediate progenitors as putative targets for cell transformation and tumor initiation (reviewed in [1]), has further heightened interest in normal MaSC properties and regulation. In contrast, limited information is available on stem cells and their progeny in the mammary glands of other species.…”

Section: Introductionmentioning

confidence: 99%

Cell Hierarchy and Lineage Commitment in the Bovine Mammary Gland

Rauner

Barash

2012

PLoS ONE

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The bovine mammary gland is a favorable organ for studying mammary cell hierarchy due to its robust milk-production capabilities that reflect the adaptation of its cell populations to extensive expansion and differentiation. It also shares basic characteristics with the human breast, and identification of its cell composition may broaden our understanding of the diversity in cell hierarchy among mammals. Here, Lin− epithelial cells were sorted according to expression of CD24 and CD49f into four populations: CD24medCD49fpos (putative stem cells, puStm), CD24negCD49fpos (Basal), CD24highCD49fneg (putative progenitors, puPgt) and CD24medCD49fneg (luminal, Lum). These populations maintained differential gene expression of lineage markers and markers of stem cells and luminal progenitors. Of note was the high expression of Stat5a in the puPgt cells, and of Notch1, Delta1, Jagged1 and Hey1 in the puStm and Basal populations. Cultured puStm and Basal cells formed lineage-restricted basal or luminal clones and after re-sorting, colonies that preserved a duct-like alignment of epithelial layers. In contrast, puPgt and Lum cells generated only luminal clones and unorganized colonies. Under non-adherent culture conditions, the puPgt and puStm populations generated significantly more floating colonies. The increase in cell number during culture provides a measure of propagation potential, which was highest for the puStm cells. Taken together, these analyses position puStm cells at the top of the cell hierarchy and denote the presence of both bi-potent and luminally restricted progenitors. In addition, a population of differentiated luminal cells was marked. Finally, combining ALDH activity with cell-surface marker analyses defined a small subpopulation that is potentially stem cell- enriched.

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“…In normal breast tissue, the MUC1 gene is expressed on the luminal surfaces of glandular epithelial cells. In accordance with its origin, MUC1 expression is more common in the luminal subtype of BC compared to the HER2-enriched or basal-like tumors [23,24], even though the subcellular localization of mucins appears to be altered in BC [16,22]. In addition, a previous study determined that MUC1 overexpression is associated with a higher estrogen receptor (ER)-positive phenotype [16], and when staining of mucin in BC cells was linked to the ER, progesterone receptor (PgR), HER2, and p53 expression, only the cytoplasmic expression of MUC1 correlated positively with ER expression [22].…”

Section: Introductionmentioning

confidence: 99%

Implications of Different CA 15-3 Levels according to Breast Cancer Subtype at Initial Diagnosis of Recurrent or Metastatic Breast Cancer

Park

Ahn²,

Park³

et al. 2012

Oncology

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Background: CA 15-3 is derived from proteolytic shedding of the extracellular domain of mucin 1 (MUC1) glycoprotein. Luminal subtype breast cancer shows a higher expression in MUC1 genes, and a positive relationship between MUC1 expression and estrogen receptor (ER) expression has been reported. In this study, we attempted to determine the difference of CA 15-3 level according to the subtype of breast cancer. Methods: From January 2000 to December 2009, a total of 707 patients who were diagnosed with metastatic or recurrent breast cancer at Samsung Medical Center were included in this study. Among these, 536 patients with available clinical data including pretreatment CA 15-3 and immunohistochemistry for ER, progesterone receptor (PgR) and hormone receptor 2 (HER2) were analyzed in this study. Patients were classified into 3 groups according to their receptor status: ER-positive (ER+) and/or PgR+ irrespective of HER2 (HR+), ER–/PgR–/HER2+ (HER2-enriched) and ER–/PgR–/HER2– (triple negative, TN). Results: The supranormal values of CA 15-3 were frequently observed in HR+ breast cancer compared to other types (45.6% for HR+, 24.4% for HER2-enriched and 28.8% for TN; p < 0.001). The increase of marker levels differed significantly among the 3 groups (24 U/ml for HR+, 13 U/ml for HER2-enriched and 18 U/ml for TN; p < 0.001). Conclusions: The increase of both marker levels and the frequency of supranormal values of CA 15-3 were more frequently observed in HR+ breast cancer, which is positively associated with MUC1 expression. These results could potentially serve as a basis for expanding the clinical implications of CA 15-3 in the field of clinical trials for novel targeted therapies in breast cancer.

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Common Molecular Mechanisms of Mammary Gland Development and Breast Cancer

Cited by 48 publications

References 103 publications

ABCG2, a novel antigen to sort luminal progenitors of BRCA1- breast cancer cells

ABCG2, a novel antigen to sort luminal progenitors of BRCA1- breast cancer cells

Cell Hierarchy and Lineage Commitment in the Bovine Mammary Gland

Implications of Different CA 15-3 Levels according to Breast Cancer Subtype at Initial Diagnosis of Recurrent or Metastatic Breast Cancer

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