Transport changes associated with growth control and malignant transformation

Abstract

We can distinguish two classes of membrane transport changes in cultured cells: (a) growth-rate contingent changes are those which occur in coordination with the onset of density-dependent inhibition of growth; (b) transformation-specific changes are those which occur when cells become transformed, and which can be detected even when normal and transformed cells are growing at the same rate. Growth-rate contingent changes include the density-dependent changes in phosphate, nucleoside, glucose, amino acid, and potassium transport. Only one transformation-specific transport change has been found in Rous-transformed chicken embryo fibroblasts: an increased rate of hexose transport. The variation in potassium transport are associated with variations in the number of ouabain binding sites in the membrane. The molecular basis for changes in the rate of hexose transport is unknown, although gross changes in membrane bilayer composition and "fluidity" seem not to be involved. In analyzing the regulation of hexose transport activity, we find that decreased cAMP may play a role in the transformation-specific increase in hexose transport, but that fibrinolytic activity is not necessary.

Effects of diamines on ornithine decarboxylase activity in control and virally transformed mouse fibroblasts

“…It is of interest that the experiment shovyn in Table 3 may indicate that SV-transformed 3T3 cells take up putrescine less rapidly than normal 3T3 cells. This result is the opposite of the well known enhanced transport of certain amino acids and sugars in virally transformed cells (Foster & Pardee, 1969;Isselbacher, 1972;Weber et al, 1976;Dubrow et al, 1978). However, it should be stressed that the uptake of radioactivity measured in the present experinments merely indicates the maximal rate of net uptakce of the added putrescine and may not reflect a true rate of transport because of complications that may arise from further metabolism, a difference in the starting intracellular putrescine concentratipn, and the possibility that some of the putrescine is merely tightly adsorbed to the cell surface.…”

“…However, the very low extracellular concentrations at which these exert effects on ornithine decarboxylase (which are substantially less than the normal intracellular concentrations, unless most of the intracellular polyamine is bound to macromolecular anions) renders this an attractive hypothesis. It is known that viral transformation of mouse fibroblasts results in the alteration of membrane characteristics including changes in the content of glycolipids, glycoproteins and surface proteins as well as changes in the transport of sugars and amino acids (Van Nest & Grimes, 1977;Weber et al, 1976;Isselbacher, 1972;Dubrow et al, 1978). It is possible that a change in the receptor site for putrescine or spermidine might be responsible for the lack of sensitivity of the SV-transformed cells.…”

Association of 82 Rubidium and 11C-methionine uptake in brain tumors measured by positron emission tomography

“…Furthermore, there is evidence of an association of potassium and amino acid transport in cultured non-brain tumor cells. The cellular uptake of K ~ and the nonmetabolized amino acid 0t-aminoisobutyric acid (~-AIB) increases around the S-G 2 interface of the cell cycle [20] and decreases when cells are inhibited for growth [21]. It has also been suggested that a single protein kinase, induced by growth factor receptor activation, regulates independently a NaCI/KCI symporter and amino acid transport systems [1].…”

Analysis of aryl hydrocarbon hydroxylase activity in human lung tissue, pulmonary macrophages, and blood lymphocytes

“…37 The fluidity of the phospholipid components in these cells is altered in such a way as to create more rigidity in the cell membranes. It is believed that the cytochrome P1-450 and the reductase portions of the AHH complex are enclosed in a phospholipid matrix within the membrane of the endoplasmic reticulum.…”