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

Bhargava, Poonam

doi:10.1016/0022-5193(77)90231-4

Cited by 22 publications

(6 citation statements)

References 290 publications

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“…The best characterized systems which are regulated by protein kinases and which are also believed to influence growth rate are presented in Table 4. Many of these serve as potential determinants of growth rate and targets on oncogene action (Russel, Byus & Manen, Bhargava, 1977;Rozengurt, 1980Rozengurt, , 1986. Indeed, extensive evidence suggests that the Na+/H § antiporter as well as the Na+,K+-ATPase are primary determinants of growth rate in many cell lines, while the glucose carrier may be a principal target of oncogene action in many others (see Table 4).…”

Section: Transport Systems As Targets Of Oncogene Actionmentioning

confidence: 97%

Neutral amino acid transport systems in animal cells: Potential targets of oncogene action and regulators of cellular growth

et al. 1988

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Section: Transport Systems As Targets Of Oncogene Actionmentioning

confidence: 97%

Neutral amino acid transport systems in animal cells: Potential targets of oncogene action and regulators of cellular growth

et al. 1988

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“…Yrevious investigators concerned with understanding the implementation, maintenance, and loss of control of cell division have suggested that cytoplasmic nutrient concentrations may play a role (Holley, 1972;Bhargava, 1977). This suggestion was derived from observations that elevated concentrations of low molecular weight nutrients enhanced growth rates (Griffiths, 1972) and promoted growth of quiescent cells (Paul and Walter, 1974).…”

mentioning

confidence: 99%

Growth regulation and amino acid transport in epithelial cells: Influence of culture conditions and transformation on A, ASC, and l transport activities

Boerner

Saier

1982

Journal Cellular Physiology

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Amino acid transport in Madin-Darby canine kidney (MDCK) cells, grown in a defined medium, was investigated as a function of cell density, exposure to specific growth factors, and transformation. MDCK cells were found to transport neutral amino acids by systems similar to the A, ASC, L, and N systems which have been characterized using other cell lines. Experimental conditions were developed for MDCK cells which allowed independent measurement of A, ASC, and L transport activities. The activity of the L system was measured as Na+-independent leucine or niethionine uptake at pH 7.4. The activity of the A system was measured as Na+-dependent a(methy1amino)isobutyric acid (mAl €3) uptake at p H 7.4, the activity of the ASC system was measured as Na+-dependent alanine uptake in the presence of 0.1 m M mAlB at pH 6.0, and the activity of system N was observed by measuring Na+-dependent glutamine uptake at pH 7.4 in the presence of high concentrations of A and ASC system substrates. The L transport system responded minimally to changes in growth state, but Na+-dependent amino acid transport responded to regulation by growth factors, cell density, and transformation. The activities of the A and ASC systems both decreased at high cell density, but these activities responded dissimilarly under other conditions. The activity of the A system was stimulated by insulin, was inhibited by PGE,, and was elevated 3-7 fold in the transformed cell line, MDCK-T,. The activity of the ASC system wa5 slightly stimulated by insulin and by PGE,, but was unchanged after chemical transformation. Changes in cellular growth were monitored and were found to correlate best with the activity of the A system. These results suggested that MDCK cell growth may be more closely related to the activity of the A than of the ASC system.

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“…The hepatocellular membrane is an important locus for the transport of substrates involved in the regulation of metabolic events related to cell differentiation, proliferation and malignancy (Holley, 1972;Bhargava, 1977). Cellular growth and proliferation are strongly associated with increased capacities to concentrate amino acids that occur particularly during the transition of the G1 to the S phase in the cell cycle.…”

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confidence: 99%

Amino acid transport and rubidium-ion uptake in monolayer cultures of hepatocytes from neonatal rats

Bellemann

1981

Biochemical Journal

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Amino acid and K(+) transport during development has been investigated in hepatocyte monolayer cultures with either alpha-amino[1-(14)C]isobutyrate or (86)Rb(+) used as a tracer for K(+). Parenchymal cells from neo- and post-natal rat livers have been isolated by an improved non-perfusion technique [Bellemann, Gebhardt & Mecke (1977)Anal.Biochem.81, 408-415], and the resulting hepatocyte suspensions purified from non-hepatocytes before inoculation. In the presence of Na(+) (Na(+)-dependent component), the rates of amino acid uptake in neonatal hepatocytes were markedly enhanced compared with cells from 30-day-old rats. When Na(+) was replaced by choline (Na(+)-independent component) the accumulation of alpha-aminoisobutyrate was decreased and it was not affected by the age of the animals. Kinetic analysis of Na(+)-dependent alpha-aminoisobutyrate transport revealed the existence of a high-affinity low-K(m) component (K(m)0.91mm) with a V(max.) of 2.44nmol/mg of protein per 4min, which later declined gradually with progressive development. Rates of Rb(+) transport were concomitantly enhanced in neonatal hepatocytes and thereafter declined with postnatal age. The increased Rb(+) influx was effectively inhibited by ouabain and reflected elevated activity of the electrogenic Na(+)/K(+)-pump during early stages of development. Kinetic evaluation of the enhanced rates of Rb(+) uptake indicates multiple and co-operative binding sites of the enzyme involved in the Rb(+) uptake, and the transport system is positively co-operative (the Hill coefficient h is >1.0). In short, amino acid transport in neonatal rat hepatocytes is increased as a result of an existing low-K(m) component for the Na(+)-dependent alpha-aminoisobutyrate uptake, which endows the hepatocytes with a high capability for concentrating amino acids at low ambient values. The concomitant enhancement of K(+) transport reflects changes in the electrochemical gradient for Na(+) across the hepatocellular membrane and, along with this, presumably alterations in the membrane potential; the latter might be the driving force for the enhanced alpha-aminoisobutyrate transport in the alanine-preferring system during postnatal age.

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

Cited by 22 publications

References 290 publications

Neutral amino acid transport systems in animal cells: Potential targets of oncogene action and regulators of cellular growth

Neutral amino acid transport systems in animal cells: Potential targets of oncogene action and regulators of cellular growth

Growth regulation and amino acid transport in epithelial cells: Influence of culture conditions and transformation on A, ASC, and l transport activities

Amino acid transport and rubidium-ion uptake in monolayer cultures of hepatocytes from neonatal rats

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