Acinar cell carcinoma of rat pancreas: Regulation of cholesterol esterification

Rao, Kalipatnapu N.; Kottapally, Sujatha; Eskander, E. D.; Shinozuka, Hisashi; Dessì, S.; Pani, P.

doi:10.1038/bjc.1986.177

Cited by 22 publications

(13 citation statements)

References 28 publications

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“…Previous studies from our and other laboratories have demonstrated that sustained processes of normal and neo plastic cell proliferation are characterized by peculiar changes in intracellular cholesterol metabolism: an in crease of cholesterol synthesis accompanied by an ac cumulation of cholesterol esters (the form in which choles terol is stored inside the cells) was observed in different models of hyperplastic and neoplastic growth, both in ex perimental animals [5,6,[15][16][17] and in humans [18]. An exception to this pattern was observed in leukemic leuko cytes in which, despite the increase in synthesis, a decrease in cholesterol content was found [19][20][21],…”

Section: Discussionmentioning

confidence: 99%

“…An increase in cholesterol es ters of about three folds was observed in lung tumor tissues when compared to the corresponding normal tissues. High levels of acyl-cholesterol acyltransferase (ACAT) activity, the intracellular esterifying enzyme for free cholesterol were also evident in different experimental models of hyperplastic and neoplastic growth [15,18,22], It has been suggested that during rapid cell proliferation cholesterol esters are trapped inside cells probably to meet the in creased demand for cholesterol for new membrane biogenesis occurring during cell proliferation. However, the possibility that cholesterol accumulation may also be due to a loss of regulation of its biosynthetic pathway should be considered, as has been suggested by various authors [2,23].…”

Section: Discussionmentioning

confidence: 99%

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Altered Pattern of Lipid Metabolism in Patients with Lung Cancer

Dessì¹,

Batetta²,

Pulisci³

et al. 1992

Oncology

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Cholesterol distribution in tumoral tissues and lipid composition in the plasma compartment were determined in patients affected by different histologic types of lung cancer. The results showed that tumoral lung tissues contained 2-fold more total cholesterol and 3.5-fold more esterified cholesterol than normal lung tissues. In the patients the alterations in intracellular cholesterol were also associated with peculiar changes in cholesterol distribution in the plasma compartment. Serum high-density lipoprotein (HDL) cholesterol levels were markedly lower in than in controls. No significant changes in other lipid parameters were observed in these patients. We suggest that the reduced levels of serum HDL cholesterol observed in patients with lung tumors may be a consequence of the disease, probably mediated by the greater utilization of cholesterol for new membrane biogenesis and by the accumulation of esterified cholesterol in tumoral tissues.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Altered Pattern of Lipid Metabolism in Patients with Lung Cancer

Dessì¹,

Batetta²,

Pulisci³

et al. 1992

Oncology

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“…An increase of free and esterified cholesterol synthesis was also found in kidney [73] and bone marrow proliferations [74] and during foetal and neonatal development [75], in pancreatic regeneration after tissue loss and in fast and slowly growing tumours [76]. In models in which parenchymal proliferation was restricted to a limited period, intracellular cholesterol synthesis and esterification were seen to preceed the onset of DNA synthesis, with a maximal increase at the peak of thymidine incorporation, and returning to baseline levels on recovery of the original parenchyma size [67,68].…”

Section: Cholesterol Metabolism In Normal and Tumour Growthmentioning

confidence: 99%

Cholesterol metabolism during cell growth: Which role for the plasma membrane?

Batetta

Sanna

2006

Euro J Lipid Sci & Tech

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Parenchyma proliferation is accompanied by a peculiar modification of the cholesterol metabolism involving both the growing tissue and the plasma compartment. The increase of cholesterol synthesis and uptake has been largely described in the literature and mainly ascribed to the increased requirement of cholesterol for new membrane biogenesis. The dramatic reduction of cholesterol efflux, which probably contributes to the increase of cholesterol esterification and accumulation, has also been largely described, although, further to acting as a prompt pool for membrane biogenesis requirements, its significance and possible influence on cholesterol homeostasis during growth has been almost completely neglected. In this short review, the most widely known modifications and new insights into the cholesterol metabolism during the growth of normal and tumoral cells will be discussed. Particular attention will be paid to the most widely known modifications of cholesterol storage and efflux. The possible implication of proteins in membrane cholesterol translocation causing cholesterol to be directed towards the ER for esterification by ACAT rather than being released by the appropriate external acceptor, i.e. HDL, during proliferation will be discussed. Keywords:Membrane cholesterol, HDL-C, cell proliferation, signal transduction. Cholesterol metabolism in non-growing cellsWith the exception of specialised cells such as hepatocytes, the majority of resting cells synthesise cholesterol only virtually, with the minimal amounts of the required sterols being obtained by an external source (via lowdensity lipoprotein (LDL) receptor), intracellular cholesterol esterification and efflux also being absent, in accordance with the low membrane turnover present in this condition. Under normal conditions, intracellular cholesterol homeostasis utilises a complex network of reactions capable of providing an adequate supply of cholesterol while avoiding possible conditions of toxicity for the cells. In the majority of cells, the cholesterol supply is regulated by the balance between endogenous synthesis in the endoplasmic reticulum (ER), under the control of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoA-R), and uptake of exogenous cholesterol, involving endocytosis of the LDL receptor (LDL-r) complex [1]. Toxic conditions produced by excess free cholesterol can be avoided in several ways: by down-regulating cholesterol synthesis and uptake, by promoting esterification by acyl-CoA:cholesterol acyltransferase (ACAT) in the ER [2], and/or by transport to the plasma membrane with subsequent delivery to an external acceptor, i.e. highdensity lipoproteins (HDL) [3].However, it is a well-established fact that a pool of cholesterol completes a cycle to the membrane and returns to the ER with a half-time of 40 min [4], and numerous studies have been undertaken to clarify the mechanisms and the proteins involved in the transport of such a highly hydrophobic lipid between the various intracellular compartments [5][6][7].With regard to cholester...

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“…Finally, there is a synchrony between de novo cholesterogenesis and DNA synthesis (Rao et al, 1984a;Siperstein, 1984). We showed that during cell proliferation there is a reduction in circulating cholesterol esters resulting in their reduced influx (Rao et al, 1986) and a stimulation of de novo cholesterogenesis and hexose monophosphate pathway (Rao et al, 1983;1984a, b;Pani et al, 1984).…”

Section: Srmlpdaayementioning

confidence: 99%

Cholestyramine promotes 7,12-dimethylbenzanthracene induced mammary cancer in Wistar rats

Melhem¹,

Gabriel²,

Eskander³

et al. 1987

Br J Cancer

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Summary The promotion of 7,12-dimethylbenzanthracene (DMBA) induced mammary cancer in Wistar rats by a 4% cholestyramine (CHST) diet was investigated. The rats, 50 days of age, were divided into six groups. First two groups were given an intragastric dose of 0.8 ml of corn oil whereas the remaining four groups were given a single intragastric dose of 5 mg of DMBA dissolved in 0.8 ml of corn oil. After 1 week on laboratory chow the first two groups and two groups treated with DMBA were fed a control diet and the two remaining groups treated with DMBA were fed a 4% CHST diet. Half the animals were killed at 100 days and the remainder at 200 days. A detailed histologic examination of grossly normal mammary tissue as well as any tumour mass was made for each rat. The serum lipids were extracted and the individual neutral lipid composition was determined. In rats treated with DMBA and fed a 4% CHST diet, the incidence of malignant tumours increased by 5 fold, and the tumour weight by 12 fold. In addition, the serum total lipids, cholesterol esters and triglycerides decreased significantly when compared with rats fed a control diet. These results suggest that CHST diet promotes DMBA cholesterol levels by 12%, resulting in a 19% reduction in At 50 days of age, they were divided into 6 groups and deaths due to coronary heart disease (CHD). Based on these subjected to the following treatments: 4 animals each in studies it has been widely accepted that a reduction in the groups a and b were given a single intragastric dose of 0.8ml serum cholesterol levels will significantly reduce the risk of corn oil alone by a stomach tube; 5 animals in group c, 7 CHD in humans (Rifkind, 1986). While this conclusion may animals in group d, 6 animals in group e, and 10 animals in be warranted, some epidemiological studies have shown that group f were each given 5 mg of DMBA dissolved in 0.8 ml a reduction in serum cholesterol levels resulted in increased of corn oil. All the animals were fed laboratory chow (Allied incidence of all cancers and colon cancer in particular Mills Inc., Chicago, IL) for the next 7 days, then switched to (Graham 1984). Some scientists concluded that treatment semipurified diets (ICN Pharmaceuticals Inc. Cleveland, with cholestyramine increases the risk for cancer (Vitale & OH). The control semipurified diet (AIN) was prepared as Ross, 1985). If indeed CHST or low serum cholesterol levels recommended by the American Institute of Nutrition (Bieri increase the risk for cancer, the mechanism by which this is et al., 1977). This diet contained 50g sucrose, 20g casein, brought about is unknown. There are only three published 15g corn starch, 0.3g methionine, 5g cellulose, 5g corn oil, reportsa which showed conclusively that CHST promotes 1 g vitamin mixture, 3.5 g mineral mixture and 0.2 g choline. cancers in rats. Nigro et al (1973) showed that at 2% level A 4% CHST diet was prepared by substituting 4 g of pure in the dietn CHST promotes colon cancer in male Sprague-cholestyramine resin (Bristol-Meyers Company,...

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Acinar cell carcinoma of rat pancreas: Regulation of cholesterol esterification

Cited by 22 publications

References 28 publications

Altered Pattern of Lipid Metabolism in Patients with Lung Cancer

Altered Pattern of Lipid Metabolism in Patients with Lung Cancer

Cholesterol metabolism during cell growth: Which role for the plasma membrane?

Cholestyramine promotes 7,12-dimethylbenzanthracene induced mammary cancer in Wistar rats

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