Cell surface changes and Rous sarcoma virus gene expression in synchronized cells.

Abstract

We have investigated whether cell surface changes associated with growth control and malignant transformation are linked to the cell cycle. Chicken embryo cells synchronized by double thymidine block were examined for cell-cycle-dependent alterations in membrane function (measured by transport of 2-deoxyglucose, uridine, thymidine, and mannitol), in cell surface morphology (examined by scanning electron microscopy), and in the ability of tumor virus gene expression to induce a transformation-specific change in membrane function. We reach the following conclusions: (a) The high rate of 2-deoxyglucose transport seen in transformed cells and the low rates of 2-deoxyglucose and uridine transport characteristic of density-inhibited cells do not occur in normal growing cells as they traverse the cell cycle. (b) Although there are cell cycle-dependent changes in surface morphology, they are not reflected in corresponding changes in membrane function. (c) Tumor virus gene expression can alter cell membrane function at any stage in the celt cycle and without progression through the cell cycle.It is widely suspected that the cell surface plays a critical role in the regulation of cell growth and metabolism, and the frequency of reports which link cell surface changes to growth control and malignant transformation support this suspicion (1-3). Changes in membrane transport are among the cell surface alterations which seem to be involved in the control of growth. For example, an increased rate of hexose transport is one of the earliest surface changes accompanying malignant transformation, and a decreased transport rate is closely associated with the onset of densitydependent inhibition of growth: exponentially growing cells display three to five times the rate of hexose transport of density-inhibited cells, while transformed cells exhibit a rate which is another three to five times that of exponentially growing cells (4-6). Rates of transport of uridine and thymidine are reduced in cells which are densityinhibited (7-9); however, no difference was noted between exponentially growing and transformed cells (5) 1. These data indicate interrelationships between the transport of small molecules and the growth state of the cell.Since density-inhibited ceils are arrested in the GI phase of the cell cycle, and since transformed cells and mitotic cells display similarities in binding of lectins to the cell surface (2, 10), one can ask whether cell surface alterations associated with growth control and malignant transformation are intrinsic to the physiological state of the celt or whether they are cell cycle dependent. For example, is the low rate of hexose, uridine, and thymidine uptake seen in density-inhibited cells a result Brady, T,, and M. J. Weber. Unpublished results. 398

Surface ruffles as markers for studies of cell transformation by Rous sarcoma virus.

“…This observation confirms the previous report (3) (9) of cells infected with wild-type RSV (Schmidt-Ruppin strain). Probably the differences in appearance of the structures seen in our electron micrographs and those of Hale et al result from the long fixation period used by them, which we have found leads to partially degraded preparations.…”

Effects of Cytochalasin B on Human Malignant

“…The cells used for the studies were in the confluent phase, 3 days after saturation, and they were stable morphologically and biologically without significant cell migration. Cells in this phase were reported to be density-inhibited and synchronized (5). The detailed methods for the light and electron microscopic studies have been described previously (6,7).…”

Glycoconjugate and adhesion molecule changes during the cell cycle in a human embryonic epithelial cell line

“…It has been shown that the surface of some monolayer cells undergoes distinct changes during the cell cycle (Rubin and Everhart, 1973;Porter et al, 1973;Hale et al, 1975). Cell-cycle related morphological changes have been described in feline lymphoid cells (Toth, 1981).…”