TY - JOUR
T1 - Immortalization protocols used in cell culture models of human breast morphogenesis
AU - Gudjonsson, T
AU - Villadsen, R
AU - Rønnov-Jessen, L
AU - Petersen, O W
N1 - Keywords: Breast; Cell Aging; Cell Culture Techniques; Cell Differentiation; Cell Line; Cell Proliferation; Cell Transformation, Neoplastic; DNA-Binding Proteins; Humans; Neoplasms; Oncogene Proteins, Viral; Papillomaviridae; Repressor Proteins; Telomerase
PY - 2004
Y1 - 2004
N2 - Defining the key players in normal breast differentiation is instrumental to understanding how morphogenesis becomes defective during breast cancer progression. During the past 2 decades much effort has been devoted to the development of technologies for purification and expansion of primary human breast cells in culture and optimizing a relevant microenvironment, which may help to define the niche that regulates breast differentiation and morphogenesis. In contrast to the general property of cancer, normal human cells have a finite lifespan. After a defined number of population doublings, normal cells enter an irreversible proliferation-arrested state referred to as replicative senescence. To overcome this obstacle for continuous long-term studies, replicative senescence can be bypassed by treatment of cells with chemical agents such as benzopyrene, by radiation or by transfection with viral oncogenes or the gene for human telomerase (human telomerase reverse transcriptase, hTERT). A drawback of some of these protocols is a concurrent introduction of chromosomal changes, which sometimes leads to a transformed phenotype and selection of a subpopulation, which may not be representative of the tissue of origin. In recent years, we have sought to establish immortalized primary breast cells, which retain crucial characteristics of their original in situ tissue pattern. This review discusses various approaches to immortalization of breast-derived epithelial and stromal cells and the application of such cell lines for studies on human breast morphogenesis.
AB - Defining the key players in normal breast differentiation is instrumental to understanding how morphogenesis becomes defective during breast cancer progression. During the past 2 decades much effort has been devoted to the development of technologies for purification and expansion of primary human breast cells in culture and optimizing a relevant microenvironment, which may help to define the niche that regulates breast differentiation and morphogenesis. In contrast to the general property of cancer, normal human cells have a finite lifespan. After a defined number of population doublings, normal cells enter an irreversible proliferation-arrested state referred to as replicative senescence. To overcome this obstacle for continuous long-term studies, replicative senescence can be bypassed by treatment of cells with chemical agents such as benzopyrene, by radiation or by transfection with viral oncogenes or the gene for human telomerase (human telomerase reverse transcriptase, hTERT). A drawback of some of these protocols is a concurrent introduction of chromosomal changes, which sometimes leads to a transformed phenotype and selection of a subpopulation, which may not be representative of the tissue of origin. In recent years, we have sought to establish immortalized primary breast cells, which retain crucial characteristics of their original in situ tissue pattern. This review discusses various approaches to immortalization of breast-derived epithelial and stromal cells and the application of such cell lines for studies on human breast morphogenesis.
U2 - 10.1007/s00018-004-4167-z
DO - 10.1007/s00018-004-4167-z
M3 - Journal article
C2 - 15526159
SN - 1023-294X
VL - 61
SP - 2523
EP - 2534
JO - EXS
JF - EXS
IS - 19-20
ER -