scholarly journals Coherent Expression Chromosome Cluster Analysis Reveals Differential Regulatory Functions of Amino-Terminal and Distal Parathyroid Hormone-Related Protein Domains in Prostate Carcinoma

2005 ◽  
Vol 2005 (4) ◽  
pp. 353-363 ◽  
Author(s):  
I. Tsigelny ◽  
D. W. Burton ◽  
Y. Sharikov ◽  
R. H. Hastings ◽  
L. J. Deftos
Keyword(s):  
Parathyroid Hormone ◽  
Cancer Cell ◽  
Prostate Carcinoma ◽  
Human Cancer ◽  
Expression Profiles ◽  
Cancer Cell Line ◽  
Biologically Active ◽  
Related Protein ◽  
Amino Terminal ◽  
Parathyroid Hormone Related Protein

Parathyroid hormone-related protein (PTHrP) has a number of cancer-related actions. While best known for causing hypercalcemia of malignancy, it also has effects on cancer cell growth, apoptosis, and angiogenesis. Studying the actions of PTHrP in human cancer is complicated because there are three isoforms and many derived peptides. Several peptides are biologically active at known or presumed cell surface receptors; in addition, the PTHrP-derived molecules can exert effects at the cell nucleus. To address this complexity, we studied gene expression in a DU 145 prostate cancer cell line that was stably transfected with control vector, PTHrP 1-173 and PTHrP 33-173. With this model, regulatory effects of the amino-terminal portion of PTHrP would result only from transduction with the full-length molecule, while effects pertaining to distal sequences would be evident with either construct. Analysis of the expression profiles by microarrays demonstrated nonoverlapping groups of differentially expressed genes. Amino-terminal PTHrP affected groups of genes involved in apoptosis, prostaglandin and sex steroid metabolism, cell-matrix interactions, and cell differentiation, while PTHrP 33-173 caused substantial increases in MHC class I antigen expression. This work demonstrates the distinct biological actions of the amino-terminus compared to distal mid-molecule or carboxy-terminal sequences of PTHrP in prostate carcinoma cells and provides targets for further study of the malignant process.

Dexamethasone regulation of parathyroid hormone-related protein (PTHrP) expression in a squamous cancer cell line

1994 ◽  
Vol 101 (1-2) ◽  
pp. 295-306 ◽  
Author(s):  
Jane A. Glatz ◽  
Joan K. Heath ◽  
Justine Southby ◽  
Leonie M. O'Keeffe ◽  
Kiriyama Takeshi ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Related Protein ◽  
Parathyroid Hormone Related Protein ◽  
Squamous Cancer ◽  
Pthrp Expression

scholarly journals Synthesis of Novel Biologically Active Proflavine Ureas Designed on the Basis of Predicted Entropy Changes

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4860
Author(s):  
Ladislav Janovec ◽  
Eva Kovacova ◽  
Martina Semelakova ◽  
Monika Kvakova ◽  
Daniel Kupka ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cell ◽  
Human Cancer ◽  
Cancer Cell Line ◽  
Biologically Active ◽  
Standard Entropy ◽  
The Novel ◽  
Urea Derivatives ◽  
Human Cancer Cell Lines ◽  
Pharmacological Model

A novel series of proflavine ureas, derivatives 11a–11i, were synthesized on the basis of molecular modeling design studies. The structure of the novel ureas was obtained from the pharmacological model, the parameters of which were determined from studies of the structure-activity relationship of previously prepared proflavine ureas bearing n-alkyl chains. The lipophilicity (LogP) and the changes in the standard entropy (ΔS°) of the urea models, the input parameters of the pharmacological model, were determined using quantum mechanics and cheminformatics. The anticancer activity of the synthesized derivatives was evaluated against NCI-60 human cancer cell lines. The urea derivatives azepyl 11b, phenyl 11c and phenylethyl 11f displayed the highest levels of anticancer activity, although the results were only a slight improvement over the hexyl urea, derivative 11j, which was reported in a previous publication. Several of the novel urea derivatives displayed GI50 values against the HCT-116 cancer cell line, which suggest the cytostatic effect of the compounds azepyl 11b–0.44 μM, phenyl 11c–0.23 μM, phenylethyl 11f–0.35 μM and hexyl 11j–0.36 μM. In contrast, the novel urea derivatives 11b, 11c and 11f exhibited levels of cytotoxicity three orders of magnitude lower than that of hexyl urea 11j or amsacrine.

Circulating levels of immunoreactive parathyroid hormone-related protein and intact parathyroid hormone in human fetuses and newborns

1996 ◽  
Vol 134 (4) ◽  
pp. 437-442 ◽  
Author(s):  
Nicholas E Papantoniou ◽  
Peter D Papapetrou ◽  
Aristidis J Antsaklis ◽  
Panayotis E Kontoleon ◽  
Spyros A Mesogitis ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Reproductive Age ◽  
Fetal Life ◽  
Intact Parathyroid Hormone ◽  
Human Fetuses ◽  
Related Protein ◽  
Amino Terminal ◽  
Parathyroid Hormone Related Protein ◽  
Circulating Levels ◽  
Immunoreactive Parathyroid Hormone

Papantoniou NE, Papapetrou PD, Antsaklis AJ, Kontoleon PE, Mesogitis SA, Aravantinos D. Circulating levels of immunoreactive parathyroid hormone-related protein and intact parathyroid hormone in human fetuses and newborns. Eur J Endocrinol 1996;134:437–42. ISSN 0804–4643 Undetectable or extremely low levels of circulating immunoreactive parathyroid hormone (PTH) have been reported in human newborns while PTH bioactivity was high. This prompted the hypothesis that the fetal calcemic hormone might be PTH-related protein. The purpose of this study was to measure circulating immunoreactive PTH-related protein in human fetuses and newborns in order to investigate this hypothesis. Parathyroid hormone-related protein (PTHrP(1–86)) and intact PTH were measured using two-site immunoradiometric assays in plasma obtained by cordocentesis from 23 fetuses (19–33 weeks of gestation), from 17 newborns at term (38–41 weeks), from their mothers and from 22 normal women of reproductive age. Plasma PTHrP was detectable in all but one of the fetuses and newborns and in all the mothers and the controls. The mean level was similar among fetuses (19–33 weeks) (0.43 ± 0.18 pmol/l), newborns (0.48 ±0.12), mothers (0.48 ±0.14) and normal controls (0.46 ± 0.09). Plasma PTH was found to be significantly higher in fetuses at midgestation (1.0 ± 0.99 pmol/l) than in the newborns (0.22 ± 0.21) (p < 0.0025); maternal PTH was significantly higher compared to fetal level at mid-gestation (2.1 ± 1.0, p < 0.01) as well as at term (2.69 ± 1.40, p < 0.001). In the control women PTH was 3.07 ± 1.25 pmol/l. These results showed that plasma amino-terminal PTHrP-(1–86)) is detectable during the second half of human fetal life and its level remains unchanged during this period of time, in contrast to changing levels of fetal plasma PTH. The relatively low PTHrP-(1–86) level that we found in the newborns is not responsible for the high PTH-like bioactivity found by some investigators in cord blood at term. Peter D Papapetrou, Second Division of Endocrinology, "Alexandra" Hospital, 80 Vas. Sofias & Lourou Streets, Athens 115 28, Greece

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