Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties

Guðjónsson, Þórarinn; Villadsen, René; Nielsen, Helga Lind; Rønnov‐Jessen, Lone; Bissell, Mina J.; Petersen, Ole W.

doi:10.1101/gad.952602

Cited by 339 publications

(366 citation statements)

References 47 publications

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“…In concordance with the above studies, we have identified a suprabasal MUC1-negative, ESApositive, and α-sm-actin-negative cell in the human breast (4). The frequency of MUC1-negative, ESA-positive cells in smears of trypsinized, uncultured cells was 8%, which agrees with previous murine data from which the estimated frequency of stem and progenitor cells was also estimated to be about 8-12% (42).…”

Section: Identification Of a Putative Stem Cell Compartment Within Thsupporting

confidence: 91%

“…This process gives rise to the airways of the lungs, the urine-collecting ducts, the prostate and salivary glands as well as the functional unit of the breast (2). There is ample evidence from both mice and humans that the two different epithelial cells that make up the TDLU, luminal epithelial and myoepithelial cells, are derived from common ancestors, namely the breast epithelial precursor cells positioned within the luminal epithelial compartment (3,4).…”

Section: Introductionmentioning

confidence: 99%

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Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia

Gudjonsson

Adriance

Sternlicht

et al. 2005

J Mammary Gland Biol Neoplasia

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The human breast epithelium is a branching ductal system composed of an inner layer of polarized luminal epithelial cells and an outer layer of myoepithelial cells that terminate in distally located terminal duct lobular units (TDLUs). While the luminal epithelial cell has received the most attention as the functionally active milk-producing cell and as the most likely target cell for carcinogenesis, attention on myoepithelial cells has begun to evolve with the recognition that these cells play an active part in branching morphogenesis and tumor suppression. A major question that has been the subject of investigation pertains to how the luminal epithelial and myoepithelial lineages are related and precisely how they arise from a common putative stem cell population within the breast. Equally important is the question of how heterotypic signaling occurs between luminal epithelial and surrounding myoepithelial cells in normal breast morphogenesis and neoplasia. In this review we discuss data from our laboratories and from others regarding the cellular origin of human myoepithelial cells, their function in maintaining tissue polarity in the normal breast, and their role during neoplasia.

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Section: Identification Of a Putative Stem Cell Compartment Within Thsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia

Gudjonsson

Adriance

Sternlicht

et al. 2005

J Mammary Gland Biol Neoplasia

Self Cite

229

211

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“…The loss of differentiation activity in this case is likely to be because of the influence of the viral oncoprotein E6E7, (35,36) although E6E7 has been shown to immortalize some cell types without loss of differentiation potential. (18,37) We have previously shown that cementoblast progenitors are present in BDFCs and that they are phenotypically different from osteoblasts. (10) In this study, we successfully isolated a cementoblast cell line, BCPb8, which seems to behave similarly to the cementum progenitors present in BDFCs, both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Immortalization of Cementoblast Progenitor Cells With Bmi-1 and TERT

Saito

Handa

Kiyono³

et al. 2005

Journal of Bone and Mineral Research

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A cementoblast progenitor cell line designated BCPb8 was successfully isolated from dental follicle cells immortalized with Bmi-1 and hTERT. BCPb8 showed the potential to differentiate into cementoblasts on implantation into immunodeficient mice. BCPb8 was confirmed to be the first established cementoblast progenitor cell line and will provide a useful model for investigating cementogenesis. Introduction:The dental follicle is the mesenchymal tissue surrounding the developing tooth germ. During tooth root development, progenitor cells present in the dental follicle are believed to play a central role in the formation of periodontal components (cementum, periodontal ligament, and alveolar bone). However, little more is known about the biology of these progenitors. Previously, we observed that cultured bovine dental follicle cells (BDFCs) contained putative cementoblast progenitors. To further analyze the biology of these cells, we attempted to isolate cementoblast progenitors from immortalized BDFC through expression of the polycomb group protein, Bmi-1, and human telomerase reverse transcriptase (hTERT). Materials and Methods: BDFCs were transduced with replication-deficient retroviruses carrying human Bmi-1(LXSN-Bmi-1), and hTERT (LXSH-hTERT) for immortalization. Single cell clones were established from immortalized BDFC, and differentiation into cementoblasts was assessed by implantation into immunodeficient mice. Results and Conclusion: BDFCs expressing Bmi-1 and hTERT showed an extended life span-90 population doublings more than normal BDFCs-and still contained cells with the potential to differentiate into cementoblasts on implantation into immunodeficient mice. From these cells, we established a clonal cell line, designated BCPb8, which formed cementum-like tissue that was reactive to the anti-cementum-specific monoclonal antibody 3G9 and expressed mRNA for bone sialoprotein, osteocalcin, osteopontin, and type I collagen on implantation. Thus, by using Bmi-1 and hTERT, we succeeded in immortalizing cementoblast progenitor cells from BDFC without affecting differentiation potential. The BCPb8 cell line is the first immortalized clonal cell line of cementoblast progenitors and could be a useful tool not only to study cementogenesis but also to develop regeneration therapy for patients with periodontitis.

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“…For example, introduction of HPV E6 and E7 into primary HMECs led to their immortalization (Wazer et al, 1995;Gudjonsson et al, 2002). In another study, introduction of Simian Virus 40 Early Region (SV40ER) and the catalytic subunit of human telomerase (hTERT) into adherent HMECs led to the generation of immortalized HMLE cells (Elenbaas et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties

et al. 2011

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Isolation, immortalization, and characterization of a human breast epithelial cell line with stem cell properties

Cited by 339 publications

References 47 publications

Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia

Myoepithelial Cells: Their Origin and Function in Breast Morphogenesis and Neoplasia

Immortalization of Cementoblast Progenitor Cells With Bmi-1 and TERT

Introduction of SV40ER and hTERT into mammospheres generates breast cancer cells with stem cell properties

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