Enhancement of ectopic β-human chorionic gonadotrophin expression by interferon-α

1989 ◽  
Vol 123 (3) ◽  
pp. 501-507 ◽  
Author(s):  
R. K. Iles ◽  
T. Chard

ABSTRACT Treatment of three β-human chorionic gonadotrophin (β-hCG)-expressing bladder tumour cell lines with interferon-α (IFN-α) (5000 U/per 106 cells) enhanced the rate of β-hCG secretion from 34·2 ±0·9 to 102·5 ± 0·1 mIU/106 cells per 72 h in cell line 5637; 111·15 ± 11·75 to 261·8± 51·75 mIU/106 cells per 72 h in cell line RT112 and 503·25 ± 28·55 to 1361·65± 110·3 mIU/106 cells per 72 h in cell line SCaBER. IFN-γ had no effect on the rate of β-hCG secretion. Both interferons reduced the growth rate of the cells: incorporation of radiolabelled thymidine was reduced by 15–45% in the presence of IFN-α and by 20–53% with IFN-γ. Enhancement of β-hCG secretion by IFN-α was dose-dependent over the range 5–50 000 U/106 cells. Analysis of cell cycle profiles by flow cytometry showed no increase in the proportion of cells in the G0G1 phase in cultures treated with IFN-α. The conceptus of some species produces substances which are either luteotrophic or anti-luteolytic. In sheep, the corpus luteum is maintained by ovine trophoblast protein-I, which has been shown to have structural homology with human IFN-α. In primates and a few other higher mammals, early pregnancy is maintained by chorionic gonadotrophin. IFN-α is also an early product of the human conceptus. We have now shown that IFN-α enhances the ectopic production of the β-subunit of hCG by bladder tumour cells. This study suggests a direct transcription/translational effect of this cytokine on the expression of a reproductive endocrine gene. Journal of Endocrinology (1989) 123, 501–507

1989 ◽  
Vol 2 (2) ◽  
pp. 113-117 ◽  
Author(s):  
R. K. Iles ◽  
B. H. Czepulkowski ◽  
B. D. Young ◽  
T. Chard

ABSTRACT The β-subunit of human chorionic gonadotrophin (hCG) is coded on chromosome 19 by the β-hCG-hLH gene cluster. Genomic DNA has been isolated from bladder tumour cell lines which ectopically express β-hCG. The β-hCG—hLH gene cluster was probed for possible rearrangement or amplification and cells karyotyped for chromosome 19 abnormalities. No rearrangement or amplification of the gene cluster and no consistent abnormalities of chromosome 19 were found. The expression of β-hCG by bladder tumours is therefore likely to be the result of altered gene regulation and not a rearrangement or amplification of this gene cluster.


1989 ◽  
Vol 2 (2) ◽  
pp. 107-112 ◽  
Author(s):  
R. K. Iles ◽  
T. Chard

ABSTRACT Material with the immunochemical characteristics of human chorionic gonadotrophin (hCG) is produced by bladder tumour cells in vitro and in vivo. In order to characterize this material further, media were collected from 17 cell cultures (three choriocarcinomas, seven bladder carcinomas and seven 'normal' urothelium). The hCG-like material was compared with pregnancy hCG and purified α- and β-subunits by specific radioimmunoassays. Media were also submitted to affinity chromatography and the fractions further analysed by SDS-PAGE and Western blotting. It was shown that both the neoplastic and normal urothelium produced only free β-subunit-like material. This urothelial 'β-hCG' has the same molecular weight and electrophoretic mobility as that present in the intact hCG of pregnancy.


Cancer ◽  
1984 ◽  
Vol 53 (4) ◽  
pp. 957-962 ◽  
Author(s):  
Jorge C. M. P. Monteiro ◽  
Keith M. Ferguson ◽  
J. Alan McKinna ◽  
W. Peter Greening ◽  
Alexander M. Neville

Author(s):  
Ingeborg H. Linskens ◽  
Marieke Levitus ◽  
Anneke Frans ◽  
Peter C.J.I. Schielen ◽  
John M.G. van Vugt ◽  
...  

Abstract: The VU University Medical Center (VUmc) was the first hospital in the Netherlands to introduce the Delfia Xpress for the analysis of free β-human chorionic gonadotrophin (β-hCG) and pregnancy associated plasma protein-A (PAPP-A) in the first trimester screening program for Down syndrome. Since then, others have implemented this system. In this study, we tested the equality of measurements for free β-hCG and PAPP-A between Delfia Xpress systems and one AutoDelfia system.: A total of 40 serum samples were aliquoted and stored at –20°C. Samples were analyzed by six Delfia Xpress systems and one AutoDelfia system over a time period of 2 years.: The relationships between free β-hCG and PAPP-A were excellent for the different Delfia Xpress systems (r>0.99, p<0.0001). For PAPP-A, the agreement between the main system at VUmc and five other systems was linear with slopes between 0.99 and 1.06. Similarly, agreement for free β-hCG was linear with slopes between 0.99 and 1.09. Likewise, agreement for PAPP-A and free β-hCG was excellent for the AutoDelfia vs. the main Delfia Xpress at the VUmc (r>0.99, p<0.0001). For both PAPP-A and free β-hCG, the relationships were linear with slopes of 1.08 and 1.07.: We demonstrate an excellent agreement for the analysis of PAPP-A and free β-hCG between Delfia Xpress systems and one AutoDelfia system.Clin Chem Lab Med 2009;47:222–6.


1987 ◽  
Vol 55 (6) ◽  
pp. 623-626 ◽  
Author(s):  
RK Iles ◽  
RTD Oliver ◽  
M Kitau ◽  
C Walker ◽  
T Chard

2015 ◽  
Vol 43 (4) ◽  
Author(s):  
Seung Mi Lee ◽  
Roberto Romero ◽  
Joong Shin Park ◽  
Piya Chaemsaithong ◽  
Jong Kwan Jun ◽  
...  

AbstractTo describe a new device for the transcervical collection of amniotic fluid (AF) in patients with ruptured membranes, and to compare the concentration of proteins in fluid retrieved by transabdominal amniocentesis and the transcervical AF collector.Paired AF samples were collected in patients with preterm prelabor rupture of membranes (PROM) (n=11) by transabdominal amniocentesis and with the transcervical AF collector (Yoon’s AF Collector™). Three proteins known to have high concentrations in AF [α-fetoprotein (AFP), β-human chorionic gonadotrophin (β-hCG), and prolactin] were measured.(1) There was a significant correlation between the concentrations of analytes in AF obtained by transabdominal amniocentesis and by the transcervical AF collector (r=0.94, P<0.001 for AFP; r=0.96, P<0.001 for β-hCG; r=0.72, P<0.05 for prolactin); (2) Bland-Altman plots showed no evidence of heteroscedasticity between transabdominal or transcervical AF concentrations of these markers.There was a strong correlation between the concentrations of proteins in AF collected by amniocentesis or with the transcervical device.


1992 ◽  
Vol 135 (3) ◽  
pp. 563-569 ◽  
Author(s):  
R. K. Iles ◽  
N. C. Wathen ◽  
D. J. Campbell ◽  
T. Chard

ABSTRACT Sixteen matched samples of first trimester amniotic fluid (AF), extraembryonic coelomic fluid (EECF) and maternal serum (MS) were assayed for intact human chorionic gonadotrophin (hCG) and free subunits. Total β-hCG (free β-subunit and intact hCG) levels in the EECF (median 410 kIU/l) were 61 times greater than levels in AF (median 6·73 kIU/l) and 2·8 times greater than in MS (median 141·5 kIU/l). Levels of intact hCG in the EECF (median 245 kIU/l) were 142 times greater than in AF (median 1·73 kIU/l) and 1·6 times greater than in MS (median 157 kIU/l). Free α-subunit levels in EECF (median 17·3 mg/l) were 66 times greater than in AF (median 0·262 mg/l) and 12 times greater than in MS (median 1·3 mg/l). Virtually all of the total β-hCG immunoreactivity in MS can be attributed to intact hCG, but only 60% of total β-hCG in the EECF and 20% of that in AF can be accounted for by the intact hormone. In both EECF and AF the free α-subunit was a major constituent; on a molar basis the ratio of free α:free β:intact hCG was 1:1·2:0·3 in AF, 1:0·6:0·5 in EECF and 1:0:5 in MS. Chromatography of MS, EECF and AF on Sephadex G-100 confirmed the hCG and subunit composition of the fluids. On the basis of these findings it seems likely that previous studies showing very high levels of hCG in AF during the first trimester may have incorrectly sampled the EECF. In reality, the levels of total hCG (and free subunits) are low in the AF, and only 20% is intact hCG. In both AF and EECF the free subunits may have been derived by dissociation of intact hormone, or possibly by independent synthesis. These and other findings suggest that either the amnion acts as a barrier to the transfer of proteins or that there may be dynamic removal from this compartment. By contrast, the EECF might act as a relatively stable reservoir for these proteins. Journal of Endocrinology (1992) 135, 563–569


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