Regulation of cell division and malignant transformation through control of uptake of essential nutrients. Demonstration of the presence in rat liver of a new type of protein inhibitor of transport of such nutrients
Bhargava, P.M.; Dwarakanath, V.N.; Prasad, K.S.
Cellular and Molecular Biology Including Cyto-Enzymology 25(2): 85-94
1979
ISSN/ISBN: 0145-5680 PMID: 535004 Document Number: 144374
The presence of a protein in rat liver was demonstrated which lowers to a resting level the enhanced rate of transport normally obtained in rapidly dividing liver-derived cells (such as cells of an ascitic liver tumor) or dispersed cells obtained from normal liver incubated in vitro at low cell concentrations. A further increase in the concentration of the inhibitor does not lead to any further lowering of the rate of transport in the systems mentioned above. This material seems to satisfy the criteria for the transport-inhibitory substance, I, previously, postulated in a model of regulation of cell division and malignant transformation. This model postulates that, in resting cells, only 1 set (sites A) of the 2 types of membrane sites proposed for transport of essential nutrients in cells of higher organisms, are open. The other set of sites, sites B, are the sites through which the major proportion of transport of essential nutrients occurs in dividing cells. Sites B, it is proposed in the model, are blocked by a transport-inhibitory substance, I, in resting cells. All triggers of cell division open up sites B by inactivating or destroying I, or by preventing its binding to its receptors on the cell surface. It is proposed that it is the opening of sites B and the resultant influx of nutrients with consequent increase in their pool size in the cells, that is responsible for switching on the program of the division cycle. All resting cells are proposed to be phenotypically I+ and all dividing cells (including malignant cells), I-. In malignant transformation, cells lose the ability to become I+ even when the trigger for cell division is no longer present in the system. The I-like substance, the first transport inhibitory protein of its kind that appears to have been described so far, has been partially purified and some of its properties studied. The demonstration of the existence of such a substance provides support to the model mentioned above.