Human platelet-derived growth factor stimulates amino acid transport and protein synthesis by human diploid fibroblasts in plasma-free media.

Owen, Albert; Geyer, Robert P.; Antoniades, Harry N.

doi:10.1073/pnas.79.10.3203

Cited by 62 publications

(25 citation statements)

References 34 publications

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“…Additionally such ligand-receptor interaction induces pleiotropic effects in the cell including enhanced glycolysis, increased amino acid transport, calcium, sodium and hydrogen ion exchange and protein synthesis (Owen et al, 1982). Another growth factor, transforming growth factor alpha (TGFa) binds to the EGFR.…”

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confidence: 99%

Growth factors in ovarian cancer

Owens

Cc²,

Leake³

1991

Br J Cancer

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Summary Epidermal growth factor and transforming growth factor alpha are two peptides which bind to the epidermal growth factor receptor. One hundred and seventy-four samples from 133 patients with ovarian cancer were examined for EGF and TGFa. EGF was detected in only 27.6% of samples while TGFa was present in 88.5%. The median values for TGFa presence were at least 10-fold greater than those of EGF. There was no statistical difference between either TGFa or EGF levels and degree of differentiation of the tumours. There was no statistical difference between stage three and four in relation to concentration of either peptide. Median concentration did not differ significantly among the histological sub-groups.Epidermal growth factor (EGF) interacts with its receptor, epidermal growth factor receptor (EGFR), initiating the responses which can lead to growth modulation. Additionally such ligand-receptor interaction induces pleiotropic effects in the cell including enhanced glycolysis, increased amino acid transport, calcium, sodium and hydrogen ion exchange and protein synthesis (Owen et al., 1982). Another growth factor, transforming growth factor alpha (TGFa) binds to the EGFR. Sporn and Roberts (1985) for pathological analysis and the other stored in sucrose/ glycerol buffer for later immunohistochemical analysis. Fresh homogenising buffer was prepared (20 mM HEPES, 2 mM EDTA and 0.5 mM PMSF adjusted to pH 7.4 with sodium hydroxide) and stored on ice. The two tumour sections, from which the samples for pathology had been removed (usually 1 g) were then cut into small 1 mm blocks, weighed and placed in a centrifuge tube on ice. Homogenising buffer (5 ml g-'wet weight) was added.The tumour was homogenised on ice with an ultra turrax (Janke & Kunkel) with 2 x 15 s bursts at maximum speed but allowing the homogenate to cool between bursts. The resulting homogenate was an even suspension devoid of clumps of tumour tissue. The homogenate was centrifuged at 1,000 g for 10 min. The resulting supematant was subjected to a higher speed spin (12,000 g for 1 h). The nuclear pellet from the first spin was resuspended in 3 ml of homogenising buffer and stored at -20°C until required for DNA analysis (Modified Burton). The supernatant from the high speed spin was added to two volumes of ice cold alcohol and this was centrifuged at 1,000 g for 30 min. The supernatant from the alcohol extraction was added to four volumes of ice cold ethyl acetate and placed in a fridge overnight (4°C). After 16 h a crude extract precipitated to the bottom of the vessel. The supernatant was discarded and the crude extract was suspended in 2 ml of 1 N acetic acid.

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confidence: 99%

Growth factors in ovarian cancer

Owens

Cc²,

Leake³

1991

Br J Cancer

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“…The time course and dose dependency were similar to those reported previously by others. 16 The amino acid uptake by PDGF-stimulated VSMCs reached a plateau at 4 hours, with maximum values of a 1.4-fold increase over controls for leucine, 1.7-fold for arginine, and 1.8-fold for proline ( Figure 1A). The uptake of all amino acids was stimulated with 1 to 5 ng/mL PDGF-BB, and higher concentrations did not further increase the uptake ( Figure 1B).…”

Section: Pdgf Stimulates Vsmc Uptake Of 3 Different Amino Acids Throumentioning

confidence: 99%

Phosphatidylinositol 3-Kinase Is Required for Growth Factor–Induced Amino Acid Uptake by Vascular Smooth Muscle Cells

Higaki

Shimokado

1999

ATVB

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Abstract-Although accumulating evidence suggests that phosphatidylinositol 3-kinase (PI3K) is a common signaling molecule for growth factor-induced amino acid uptake by the cell, the role of PI3K in the uptake of different amino acids was not tested under the same conditions. In this study, we asked whether PI3K mediates platelet-derived growth factor (PDGF) -stimulated uptake of different amino acids that are taken up through 3 major amino acid transporters expressed in rat vascular smooth muscle cells and other cell types and whether PI3K mediates amino acid uptake stimulated with different growth factors and vasoactive substances. PDGF increased the uptake of [ 3 H]leucine, [3 H]proline, and [ 3 H]arginine in a dose-and time-dependent fashion. Two different PI3K inhibitors, wortmannin (100 nmol/L) and LY294002 (10 mol/L), completely inhibited the amino acid uptake stimulated by PDGF. Chinese hamster ovary cells expressing both PDGF receptor-␤ and a dominant-negative PI3K did not increase their leucine uptake when stimulated with PDGF, whereas the same cells expressing only PDGF receptor-␤ did. Transforming growth factor-␤, as well as insulin-like growth factor-I and angiotensin II, increased leucine uptake by vascular smooth muscle cells. Wortmannin and LY294002 inhibited this increase. We also found that transforming growth factor-␤ stimulated PI3K activity and the phosphorylation of Akt, a downstream signaling molecule of PI3K. A similar effect of PI3K inhibitors on amino acid uptake was observed in Swiss 3T3 cells. We conclude that PI3K mediates the uptake of different amino acids by vascular smooth muscle cells and other cell types stimulated with a variety of growth factors, including transforming growth factor-␤. Our findings suggest that PI3K may play an important role in vascular pathophysiology by regulating amino acid uptake. Key Words: phosphatidylinositol 3-kinase Ⅲ amino acid uptake Ⅲ platelet-derived growth factor Ⅲ transforming growth factor-␤

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“…Besides growth, the cellular effects of PDGFs include chemotaxis (Grotendorst et al 1982;Siegbahn et al 1990), differentiation (Raff 1989;Richardson 1990), and modulation of other cell functions such as the production of extracellular matrix components (Owen et al 1982;Majack et al 1985) and contraction (Berk et al 1986;Gullberg et al 1990). Following its identification as a secretory product of platelets (Balk 1971;Busch et al 1976), PDGFs have been shown to be synthesized by numerous normal cell types, including endothelial cells, monocytes/macrophages, smooth muscle cells, fibroblasts, placenta cytotrophoblasts, neurons, and certain glial cells (for review, see Heldin and Westermark 1990;Raines et al 1990;Raines and Ross 1993).…”

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confidence: 99%

Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities.

Leveén¹,

Pekny²,

et al. 1994

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Platelet-derived growth factor (PDGF) affects the growth, migration, and function in vitro of mesenchymal cells, but little is known about its normal physiological functions in vivo. We show here that mice deficient for PDGF B die perinatally and display several anatomical and histological abnormalities. Kidney glomerular tufts do not form, apparently because of absence of mesangial cells. Instead, a single or a few distended capillary loops fill the glomerular space. The heart and some large arteries dilate in late-stage embryos. Most PDGF B mutant embryos develop fatal hemorrhages just prior to birth. Their hematological status includes erythroblastosis, macrocytic anemia, and thrombocytopenia. On the basis of these findings, we conclude that PDGF B has crucial roles in vivo in establishing certain renal and circulatory functions.

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Human platelet-derived growth factor stimulates amino acid transport and protein synthesis by human diploid fibroblasts in plasma-free media.

Cited by 62 publications

References 34 publications

Growth factors in ovarian cancer

Growth factors in ovarian cancer

Phosphatidylinositol 3-Kinase Is Required for Growth Factor–Induced Amino Acid Uptake by Vascular Smooth Muscle Cells

Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities.

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