Increased growth rate, Delayed senescense and decreased serum dependence characterize cables-deficient cells

Abstract

Cables (Cables1), a recently described growth suppressor protein that maps to human chromosome 18q 11-12, is lost in many primary colon, lung, and gynecological malignancies. Cultured cell lines that over-express 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 over-expression 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.