scholarly journals Bringing androgens up a NOTCH in breast cancer

2014 ◽  
Vol 21 (4) ◽  
pp. T183-T202 ◽  
Author(s):  
Gerard A Tarulli ◽  
Lisa M Butler ◽  
Wayne D Tilley ◽  
Theresa E Hickey
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Normal Breast ◽  
Notch Signalling ◽  
Breast Development ◽  
Breast Epithelium ◽  
Breast Epithelial Cells ◽  
Androgen Action ◽  
Breast Epithelial

While it has been known for decades that androgen hormones influence normal breast development and breast carcinogenesis, the underlying mechanisms have only been recently elucidated. To date, most studies have focused on androgen action in breast cancer cell lines, yet these studies represent artificial systems that often do not faithfully replicate/recapitulate the cellular, molecular and hormonal environments of breast tumoursin vivo. It is critical to have a better understanding of how androgens act in the normal mammary gland as well as inin vivosystems that maintain a relevant tumour microenvironment to gain insights into the role of androgens in the modulation of breast cancer development. This in turn will facilitate application of androgen-modulation therapy in breast cancer. This is particularly relevant as current clinical trials focus on inhibiting androgen action as breast cancer therapy but, depending on the steroid receptor profile of the tumour, certain individuals may be better served by selectively stimulating androgen action. Androgen receptor (AR) protein is primarily expressed by the hormone-sensing compartment of normal breast epithelium, commonly referred to as oestrogen receptor alpha (ERa (ESR1))-positive breast epithelial cells, which also express progesterone receptors (PRs) and prolactin receptors and exert powerful developmental influences on adjacent breast epithelial cells. Recent lineage-tracing studies, particularly those focussed on NOTCH signalling, and genetic analysis of cancer risk in the normal breast highlight how signalling via the hormone-sensing compartment can influence normal breast development and breast cancer susceptibility. This provides an impetus to focus on the relationship between androgens, AR and NOTCH signalling and the crosstalk between ERa and PR signalling in the hormone-sensing component of breast epithelium in order to unravel the mechanisms behind the ability of androgens to modulate breast cancer initiation and growth.

scholarly journals Expression of estrogen receptor β isoforms in normal breast epithelial cells and breast cancer: regulation by methylation

Oncogene ◽  
2003 ◽  
Vol 22 (48) ◽  
pp. 7600-7606 ◽  
Author(s):  
Chunyan Zhao ◽  
Eric W-F Lam ◽  
Andrew Sunters ◽  
Eva Enmark ◽  
Manuela Tamburo De Bella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Epithelial Cells ◽  
Normal Breast ◽  
Estrogen Receptor Β ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Normal Breast Epithelial Cells

Normal Breast Epithelial Cells Induce Apoptosis of MCF-7 Breast Cancer Cells through a p53-Mediated Pathway

2000 ◽  
Vol 3 (6) ◽  
pp. 338-344 ◽  
Author(s):  
Robert-Alain Toillon ◽  
Eric Adriaenssens ◽  
Danièle Wouters ◽  
Severine Lottin ◽  
Bénoni Boilly ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Normal Breast ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Normal Breast Epithelial Cells ◽  
Mcf 7

scholarly journals Normal and tumor-derived myoepithelial cells differ in their ability to interact with luminal breast epithelial cells for polarity and basement membrane deposition

2002 ◽  
Vol 115 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Thorarinn Gudjonsson ◽  
Lone Rønnov-Jessen ◽  
René Villadsen ◽  
Fritz Rank ◽  
Mina J. Bissell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Basement Membrane ◽  
Specific Antigen ◽  
Myoepithelial Cells ◽  
Normal Breast ◽  
Breast Epithelial ◽  
Luminal Epithelial Cells ◽  
Laminin 1

The signals that determine the correct polarity of breast epithelial structures in vivo are not understood. We have shown previously that luminal epithelial cells can be polarized when cultured within a reconstituted basement membrane gel. We reasoned that such cues in vivo may be given by myoepithelial cells. Accordingly, we used an assay where luminal epithelial cells are incorrectly polarized to test this hypothesis. We show that culturing human primary luminal epithelial cells within collagen-I gels leads to formation of structures with no lumina and with reverse polarity as judged by dual stainings for sialomucin, epithelial specific antigen or occludin. No basement membrane is deposited, and β4-integrin staining is negative. Addition of purified human myoepithelial cells isolated from normal glands corrects the inverse polarity, and leads to formation of double-layered acini with central lumina. Among the laminins present in the human breast basement membrane (laminin-1, -5 and -10/11), laminin-1 was unique in its ability to substitute for myoepithelial cells in polarity reversal.Myoepithelial cells were purified also from four different breast cancer sources including a biphasic cell line. Three out of four samples either totally lacked the ability to interact with luminal epithelial cells, or conveyed only correction of polarity in a fraction of acini. This behavior was directly related to the ability of the tumor myoepithelial cells to produce α-1 chain of laminin. In vivo, breast carcinomas were either negative for laminin-1 (7/12 biopsies) or showed a focal, fragmented deposition of a less intensely stained basement membrane (5/12 biopsies). Dual staining with myoepithelial markers revealed that tumor-associated myoepithelial cells were either negative or weakly positive for expression of laminin-1, establishing a strong correlation between loss of laminin-1 and breast cancer. We conclude that the double-layered breast acinus may be recapitulated in culture and that one reason for the ability of myoepithelial cells to induce polarity is because they are the only source of laminin-1 in the breast in vivo. A further conclusion is that a majority of tumor-derived/-associated myoepithelial cells are deficient in their ability to impart polarity because they have lost their ability to synthesize sufficient or functional laminin-1. These results have important implications for the role of myoepithelial cells in maintenance of polarity in normal breast and how they may function as structural tumor suppressors.

Normal Breast Epithelial Cells Induce Apoptosis of Breast Cancer Cells via Fas Signaling

2002 ◽  
Vol 275 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Robert-Alain Toillon ◽  
Simon Descamps ◽  
Eric Adriaenssens ◽  
Jean-Marc Ricort ◽  
David Bernard ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Normal Breast ◽  
Breast Epithelial Cells ◽  
Fas Signaling ◽  
Breast Epithelial ◽  
Normal Breast Epithelial Cells

scholarly journals bFGF and aFGF induce membrane ruffling in breast cancer cells but not in normal breast epithelial cells: FGFR-4 involvement

1995 ◽  
Vol 306 (2) ◽  
pp. 609-616 ◽  
Author(s):  
C L Johnston ◽  
H C Cox ◽  
J J Gomm ◽  
R C Coombes
Keyword(s):  
Breast Cancer ◽  
Growth Factors ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Physiological Role ◽  
Normal Breast ◽  
Breast Cancer Cell Lines ◽  
Breast Epithelial Cells ◽  
Membrane Ruffling ◽  
Breast Epithelial

Acidic and basic fibroblast growth factors (aFGF and bFGF) are growth factors which may have a physiological role in the normal breast and in breast cancer. A study of the effects of aFGF and bFGF on a variety of breast cell lines and epithelial cells purified from normal breast organoids showed that whereas normal breast cells did not exhibit membrane ruffling in response to either of these growth factors, some breast cancer cell lines did. This difference was not due to lack of receptor since all the cell lines tested were mitogenically stimulated by bFGF. Dominant negative mutations of FGF receptor 3 (FGFR-3) and the small GTP-binding protein p21rac inhibited membrane ruffling, showing that receptor dimerization and phosphorylation and p21rac activation are prerequisites for membrane ruffling in response to aFGF and bFGF. Transient transfection of individual FGFRs into cos-7 cells showed that FGFR-1, FGFR-2 and FGFR-3 could not mediate a membrane ruffling response whereas FGFR-4 could. These studies elucidate one signalling mechanism of FGF and point to differences in the response of normal and cancer breast epithelial cells which may be important in cell motility.

scholarly journals BRCA 1 promoter methylation of normal breast epithelial cells as a possible precursor for BRCA 1 ‐methylated breast cancer

2014 ◽  
Vol 105 (10) ◽  
pp. 1369-1376 ◽  
Author(s):  
Yoko Otani ◽  
Tomohiro Miyake ◽  
Naofumi Kagara ◽  
Masafumi Shimoda ◽  
Yasuto Naoi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Promoter Methylation ◽  
Normal Breast ◽  
Breast Epithelial Cells ◽  
Brca 1 ◽  
Breast Epithelial ◽  
Normal Breast Epithelial Cells
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