Stem cells and breast cancer: A field in transit

Smalley, Matthew J.; Ashworth, Alan

doi:10.1038/nrc1212

Cited by 329 publications

(288 citation statements)

References 73 publications

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“…The identical cell provides maintenance of the stem cell compartment. The distinct cell goes through a series of cell divisions and differentiation steps to generate the terminally differentiated cell populations (Smalley and Ashworth, 2003). Consistent with this concept, we demonstrated that Ck6a+ cells were able to co-express cytokeratin 19 or ZO-1.…”

Section: Discussionsupporting

confidence: 81%

“…Classically defined stem cells have a capacity to generate daughter cells that can differentiate into several cell lineages to form all the cell types that constitute the mature epithelium (Smalley and Ashworth, 2003). A stem cell might go through an asymmetric cell division to generate one cell that is identical to itself and one cell that is distinct.…”

Section: Discussionmentioning

confidence: 99%

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Identification of a stem cell candidate in the normal human prostate gland

Schmelz

Moll

Hesse

et al. 2005

European Journal of Cell Biology

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Stem cells of the human prostate gland have not yet been identified utilizing a structural biomarker. We have discovered a new prostatic epithelial cell phenotype-expressing cytokeratin 6a (Ck6a+ cells). The Ck6a+ cells are present within a specialized niche in the basal cell compartment in fetal, juvenile and adult prostate tissue, and within the stem cell-enriched urogenital sinus. In adult normal prostate tissue, the average abundance of Ck6a+ cells was 4.9%. With proliferative stimuli in the prostate organ culture model, in which the epithelial-stromal interaction was maintained, a remarkable increase of Ck 6a expression was noticed to up to 64.9%. The difference in cytokeratin 6a expression between the normal adult prostate and the prostate organ culture model was statistically significant (p<0.0001). Within the prostate organ culture model the increase of cytokeratin 6a-expressing cells significantly correlated with increased proliferation index (r = 0.7616; p = 0.0467) The Ck6a+ cells were capable of differentiation as indicated by their expression of luminal cell markers such as ZO-1 and prostate specific antigen (PSA). Our data indicate that Ck6a+ cells represent a prostatic epithelial stem cell candidate possessing high potential for proliferation and differentiation. Since the development of benign prostatic hyperplasia and prostate carcinogenesis are disorders of proliferation and differentiation, the Ck6a+ cells may represent a major element in the development of these diseases.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Identification of a stem cell candidate in the normal human prostate gland

Schmelz

Moll

Hesse

et al. 2005

European Journal of Cell Biology

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“…This implies that mammary SRBPs may represent a site of initiation of breast carcinogenesis, and is consistent with studies indicating that breast cancer initiation is a consequence of unregulated self-renew (Al-Hajj et al, 2003). Abundant evidence supports the existence of SRBPs in the mammary gland (Chepko and Smith, 1999;Smith and Chepko, 2001;Smalley and Ashworth, 2003) and progress towards their isolation and characterization Dontu et al, 2003;Trosko and Chang, 2003;Welm et al, 2003) has steadily improved our understanding of mammary gland development, cellular stasis and breast cancer initiation.…”

Section: Introductionsupporting

confidence: 68%

“…During reproductive life the epithelial portion of the mammary gland undergoes periodic and successive regenerative cycles of proliferation and cell death (Smalley and Ashworth, 2003). The periodicity of these cycles suggests a correlation between the number of regenerative cycles, the length of reproductive life and breast cancer risk.…”

Section: Introductionmentioning

confidence: 99%

TA-p63-γ regulates expression of ΔN-p63 in a manner that is sensitive to p53

Cherukuri

et al. 2005

Oncogene

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Genetic analysis indicates that TP63 is required for establishment and preservation of self-renewing progenitors within the basal layer of several epithelial structures, however, the specific contributions of transactivating (TAp63) and dominant-negative (DN-p63) isoforms remain largely undefined. Recent studies have suggested a model in which TA-p63 plays an important role in the establishment of progenitor populations in which expression of DNp63 contributes to the preservation of self-renewing capacity. Our previous studies indicate that DN-p63 is a transcriptional target of p53, however, the absence of overt epithelial deficiencies in p53À/À mice and reports of increased expression of DN-p63 in p53À/À mice suggest p53-independent mechanisms also contribute to expression of DN-p63. Here, we present data indicating that, prolonged loss of p53 leads to the activation of a p53-independent mechanism for transcriptional regulation of DN-p63. This p53-independent mechanism is sensitive to ectopic p53 but not to a p53 mutant that lacks the transactivation domain. We further show that in cells in which p53 is expressed TA-p63-c protein is destabilized in a manner that is p53 dependent and sensitive to pharmacologic inhibition of the 26S proteosome. Consistent with this observation, we demonstrate that loss of p53 leads to the stabilization of TA-p63-c that is reversible by ectopic p53. Finally, we present evidence that disruption of TA-p63-c expression leads to decreased expression of DN-p63 and that overexpression of TA-p63-c was sufficient to enhance the activity of the DN-p63 promoter. Taken together, our studies indicate that TAp63-c is capable of activating expression of DN-p63 and that this mechanism may account for p53-independent expression of DN-p63.

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“…These cells are bipotential, giving rise to luminal and myoepithelial cells [127,128]. In murine mammary glands the SP fraction is enriched for stem cells, determined by the proportion of LRCs and the ability to repopulate 'cleared' (indigenous epithelial cells removed to allow engraftment of transplanted cells) mammary fat pads in vivo with both myoepithelial and luminal lineages [129].…”

Section: Mammary Glandsmentioning

confidence: 99%

Attributes of adult stem cells

Alison

Islam

2008

The Journal of Pathology

153

115

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While cultured embryonic stem (ES) cells can be harvested in abundance and appear to be the most versatile of cells for regenerative medicine, adult stem cells also hold promise, but the identity and subsequent isolation of these comparatively rare cells remains problematic in most tissues, perhaps with the notable exception of the bone marrow. The ability to continuously self-renew and produce the differentiated progeny of the tissue of their location are their defining properties. Identifying surface molecules (markers) that would aid in stem cell isolation is a major goal. Considerable overlap exists between different putative organspecific stem cells in their repertoire of gene expression, often related to self-renewal, cell survival and cell adhesion. More robust tests of 'stemness' are now being employed, using lineage-specific genetic marking and tracking to show production of long-lived clones and multipotentiality in vivo. Moreover, the characterization of normal stem cells in specific tissues may provide a dividend for the treatment of cancer. The successful treatment of neoplastic disease may well require the specific targeting of neoplastic stem cells, cells that may well have many of the characteristics of their normal counterparts.

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Stem cells and breast cancer: A field in transit

Cited by 329 publications

References 73 publications

Identification of a stem cell candidate in the normal human prostate gland

Identification of a stem cell candidate in the normal human prostate gland

TA-p63-γ regulates expression of ΔN-p63 in a manner that is sensitive to p53

Attributes of adult stem cells

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