Production of parathyroid hormone-like peptide in a human osteosarcoma cell line: stimulation by phorbol esters and epidermal growth factor

1989 ◽  
Vol 122 (1) ◽  
pp. 219-NP ◽  
Author(s):  
S. B. Rodan ◽  
G. Wesolowski ◽  
J. Ianacone ◽  
M. A. Thiede ◽  
G. A. Rodan
Keyword(s):  
Parathyroid Hormone ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adenylate Cyclase ◽  
Cell Line ◽  
Phorbol Esters ◽  
Osteosarcoma Cell ◽  
Mrna Levels ◽  
Human Osteosarcoma ◽  
Epidermal Growth

ABSTRACT A clonal cell line (Saos-2/B-10) derived from human osteosarcoma Saos-2 cells had the same osteoblastic characteristics as the mother line, but lacked sensitivity to parathyroid hormone (PTH) at early passages. At later passages (> 70) the cells became very sensitive to PTH (0·1 nmol/l). The absence of PTH-stimulatable adenylate cyclase correlated with the secretion of an adenylate cyclase-stimulatory activity which had the properties of the recently characterized PTH-like peptide (PTH-LP). This activity was inhibited by the PTH antagonist [8norleucyl, 18norleucyl, 34tyrosinyl]bovine PTH-(3–34)amide and could be neutralized by an antiserum raised against the synthetic PTH-LP-(1–34). Hybridization with a human PTH-LP cDNA showed that these cells produce two PTH-LP mRNAs of approximately 1·5 and 1·8 kb. The production of PTH-LP was stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA; 150 nmol/l) and epidermal growth factor (EGF; 10 ng/ml). The increased accumulation of PTH-LP in conditioned media in response to TPA was seen after 1 h and levelled off at 6 h. In contrast, EGF stimulation was lower at 3 and 6 h but continued for 24 h. Both agents increased PTH-LP mRNA levels in Saos-2/B-10 cells. A TPA analogue which does not stimulate protein kinase C had no effect on PTH-LP production. Cycloheximide blocked the stimulatory effect of both TPA and EGF and the TPA effect was blocked by actinomycin D, suggesting transcriptional control. The regulation of PTH-LP by these agents may offer clues regarding the association of this protein with malignancy. Journal of Endocrinology (1989) 122, 219–227

Renal synthesis of epidermal growth factor is unchanged by vitamin D deficiency

1990 ◽  
Vol 68 (6) ◽  
pp. 733-736 ◽  
Author(s):  
Paul R. Goodyer ◽  
Sharon Langshur ◽  
Jehane Fata
Keyword(s):  
Vitamin D ◽  
Parathyroid Hormone ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Vitamin D Deficiency ◽  
Thick Ascending Limb ◽  
Mrna Levels ◽  
Luminal Membrane ◽  
Calcium Reabsorption ◽  
Epidermal Growth

In mammalian kidney, epidermal growth factor (EGF) is produced as a small internal domain of an abundant high molecular weight peptide associated with the luminal membrane of the thick ascending limb of Henle's loop and distal convoluted tubule. At present, there is no evidence to indicate a mitogenic function for the EGF-containing molecule in kidney; consideration of its molecular structure suggests the possibility of a membrane-associated physiologic role. In this study, we examine regulation of renal EGF synthesis during induction of vitamin D deficiency in mice. Despite evidence of marked hyperparathyroidism, urinary excretion of EGF was equivalent in control (2.54 ± 0.72 μg/mg creatinine) and vitamin D deficient (2.13 ± 0.97 μg/mg creatinine) animals. Similarly, EGF mRNA levels in kidney were comparable in the two groups. These data indicate that parathyroid hormone has no effect on renal EGF regulation, although it is known to stimulate calcium reabsorption in distal nephron segments.Key words: epidermal growth factor, vitamin D, calcium, kidney, parathyroid hormone.

Epidermal growth factor decreases PEPT2 transport capacity and expression in the rat kidney proximal tubule cell line SKPT0193 cl.2

2004 ◽  
Vol 286 (2) ◽  
pp. F385-F393 ◽  
Author(s):  
Silvina A. Bravo ◽  
Carsten Uhd Nielsen ◽  
Jan Amstrup ◽  
Sven Frokjaer ◽  
Birger Brodin
Keyword(s):  
Cell Culture ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Proximal Tubule ◽  
Cell Line ◽  
Proximal Tubule Cell ◽  
Mrna Levels ◽  
Transport Capacity ◽  
Tubule Cell ◽  
Epidermal Growth

The renal peptide transporter PEPT2 plays an important role in absorption of di- and tripetides in the proximal tubule; however, knowledge of regulation of PEPT2 by growth factors and hormones is limited. In the present study, we examined the effects of epidermal growth factor (EGF) on PEPT2 transport capacity and expression in the rat proximal tubule cell line SKPT0193 cl.2 (SKPT), which expresses rat PEPT2 (rPEPT2) in the apical membrane. Treatment of SKPT cells with EGF during cell culture growth caused a dose-dependent decrease in rPEPT2 transport capacity and expression, as determined by studies of apical uptake of [14C]glycylsarcosine, rPepT2 mRNA levels, and immunostaining of SKPT cells with a rPEPT2-specific antibody. On the contrary, apical uptake of glucose and lysine was increased in EGF-treated cells, indicating that EGF was not acting generally to decrease apical nutrient uptake mechanisms in the proximal tubule cells. Our findings indicate that EGF decreases rPEPT2 expression by lowering transcription of the rat PepT2 gene or by decreasing rat PepT2 mRNA stability. Previous investigators routinely used SKPT cell culture media with a high (10 ng/ml) EGF concentration. Our study suggests that this might be disadvantageous when studying PEPT2-mediated transport phenomena. These findings demonstrate for the first time EGF-mediated regulation of PEPT2 expression in a kidney cell line. The relevance for kidney regulation of peptide transport activity in physiological and/or pathophysiological situations, where EGF and EGF receptor levels change drastically, remains to be established.

scholarly journals Molecular Engineering of Curcumin, an Active Constituent of Curcuma longa L. (Turmeric) of the Family Zingiberaceae with Improved Antiproliferative Activity

Plants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1559
Author(s):  
Amena Ali ◽  
Abuzer Ali ◽  
Abu Tahir ◽  
Md. Afroz Bakht ◽  
Salahuddin ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Molecular Docking ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Cell Line ◽  
Antiproliferative Activity ◽  
Growth Factor Receptor ◽  
Molecular Engineering ◽  
Curcumin Analogs ◽  
Epidermal Growth

Cancer is the world’s second leading cause of death, accounting for nearly 10 million deaths and 19.3 million new cases in 2020. Curcumin analogs are gaining popularity as anticancer agents currently. We reported herein the isolation, molecular engineering, molecular docking, antiproliferative, and anti-epidermal growth factor receptor (anti-EGFR) activities of curcumin analogs. Three curcumin analogs were prepared and docked against the epidermal growth factor receptor (EGFR), revealing efficient binding. Antiproliferative activity against 60 NCI cancer cell lines was assessed using National Cancer Institute (NCI US) protocols. The compound 3b,c demonstrated promising antiproliferative activity in single dose (at 10 µM) as well as five dose (0.01, 0.10, 1.00, 10, and 100 µM). Compound 3c inhibited leukemia cancer panel better than other cancer panels with growth inhibition of 50% (GI50) values ranging from 1.48 to 2.73 µM, and the most promising inhibition with GI50 of 1.25 µM was observed against leukemia cell line SR, while the least inhibition was found against non-small lung cancer cell line NCI-H226 with GI50 value of 7.29 µM. Compounds 3b,c demonstrated superior antiproliferative activity than curcumin and gefitinib. In molecular docking, compound 3c had the most significant interaction with four H-bonds and three π–π stacking, and compound 3c was found to moderately inhibit EGFR. The curcumin analogs discovered in this study have the potential to accelerate the anticancer drug discovery program.

Epidermal growth factor receptors and adenylate cyclase activity in human thyroid tissues

1990 ◽  
Vol 14 (3) ◽  
pp. 410-417 ◽  
Author(s):  
Quan-Yang Duh ◽  
Allan E. Siperstein ◽  
Rebecca A. Miller ◽  
Joan J. Sancho ◽  
Michael J. Demeure ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Adenylate Cyclase ◽  
Growth Factor Receptors ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Human Thyroid ◽  
Epidermal Growth Factor Receptors ◽  
Epidermal Growth
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