Increased growth rate, delayed senescense and decreased serum dependence characterize cables-deficient cells.
Cables (Cables1), a recently described growth suppressor protein that maps to human chromosome 18q11-12, is lost in many primary colon, lung, and gynecological malignancies. Cultured cell lines that overexpress Cables show a reduction in cell proliferation and Cables(-/-) mice are viable with normal embryonic development. Since Cables expression is lost in primary human tumors and overexpression of Cables suggests a role in growth suppression, we investigated growth properties of primary mouse embryonic fibroblasts (MEFs) from Cables(-/-) and Cables(+/+) mice. Cables(-/-) MEFs exhibited a doubling time of 43-45 hours compared to 73-75 hours for the Cables(+/+)MEFs. Similarly, Cables(-/-) MEFs show a delayed onset of senescence and extension of lifespan, while the Cables(+/+) MEFs ceased proliferating after eight cumulative population doublings. Cables(-/-) MEFs were able to proliferate in low serum concentrations. These data provide convincing evidence that Cables plays a role in the regulation of cell proliferation and survival.
Kirley
Sandra D
SD
Department of Urology and Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA. skirley@partners.org
Rueda
Bo R
BR
Chung
Daniel C
DC
Zukerberg
Lawrence R
LR
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002417:Cattle; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D005312:Fetal Blood / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*
C411580:Cables1 protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D010750:Phosphoproteins