Enhanced proliferative potential in culture of cells from p53-deficient mice.
Normal somatic cells are endowed with limited doubling potential in culture, and the process of immortalization is an inevitable step in neoplastic transformation of the cells. To examine the roles of p53 in this process, the cells of p53-deficient mice were examined for doubling potential. Fibroblast-like cells from a variety of tissues of these mice proliferated continuously without showing aging or crisis. The aneuploid cells overcome the population with passage, but cloning experiment indicated that chromosomal changes were not essential to this process. The enhanced proliferative potential in culture of cells from the p53-deficient mice was also observed in epithelial cells of lens, mammary glands and seminal vesicles and in neural precursor cells. Proliferation of bone marrow cells in response to stem cell factor was enhanced in long term culture, but not in in vitro colony assay; no permanent cell lines could be obtained. No effects of p53-deficiency were found in proliferation of cardiac muscle cells or hepatocytes.
Tsukada
T
T
Laboratory of Molecular Oncology, Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Japan.
Tomooka
Y
Y
Takai
S
S
Ueda
Y
Y
Nishikawa
S
S
Yagi
T
T
Tokunaga
T
T
Takeda
N
N
Suda
Y
Y
Abe
S
S
D000782:Aneuploidy; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D015153:Blotting, Western; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D002678:Chimera; D002875:Chromosomes / Q000648:ultrastructure; D004247:DNA / Q000032:analysis / Q000235:genetics; D004847:Epithelial Cells; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005434:Flow Cytometry; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D007621:Karyotyping; D007908:Lens, Crystalline / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010641:Phenotype; D011003:Ploidies; D016133:Polymerase Chain Reaction; D012669:Seminal Vesicles / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D019089:Stem Cell Factor; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor; D016159:Tumor Suppressor Protein p53; D004247:DNA