Regulation of cell division and malignant transformation. A new model for control by uptake of nutrients

| March 22, 2015 | 0 Comments


Published in: Journal of Theoretical Biology. 1977, 68, 101-137.


A comprehensive model of regulation of normal growth and of malignant transformation is presented. The model postulates four chemical (I, Anti-I, SFl and SF2) and two structural (Sites A and Sites B) entities. Sites A and B are functionally different transport sites on the membrane for essential nutrients. Sites A are open in resting cells and need a serum factor, SFl, for operation at V max. Sites B are closed in resting cells but open in dividing cells; the “on→off” control of Sites B is achieved through I, a protein with a high rate of turnover and two binding sites. Sites B are closed when I is bound to them; the affinity of I for Sites B increases when one molecule of I links two Sites B. A second serum factor (SF2), Anti-I when released from the cells (e.g. as a result of tissue damage), and other external triggers for cell division (such as mitogenic hormones), destroy or inactivate I, or prevent its binding to Sites B. The opening of Sites B results in an enhancement of the rate of uptake of nutrients; the resulting increase in the intracellular concentration of one or more of the nutrients starts the programmed operation of events that culminate in cell division; two possible mechanisms for the initiation of this programme are suggested. Growth ceases as a consequence of re-establishment of I function on the membrane. Malignant transformation is defined as an inheritable intracellular event, spontaneous or induced, which interferes with the production or activity of I and leads to a loss of the capacity for transition from the dividing to the resting state. Likely candidates for the various entities proposed are listed.

PMID: 535004| DOI:

Biological Transport, Cell Division, Cell Transformation, Neoplastic, Liver/analysis, Liver/metabolism, Liver Neoplasms, Experimental/metabolism, Proteins/pharmacology, Proteins/physiology


Regulation of cell division and malignant transformation. A new model for control by uptake ofnutrients. P M BHARGAVA. Journal of Theoretical Biology. 1977, 68, 101-137.


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