Downregulation of protein kinase C by phorbol ester increases expression of epidermal growth factor receptors in transformed trophoblasts and amplifies human chorionic gonadotropin production.

Abstract:

:Epidermal growth factor (EGF) and its homologue, transforming growth factor-alpha (TGF-alpha), regulate human chorionic gonadotropin (hCG) synthesis in the human placenta. The current study was designed to investigate the involvement of the protein kinase C pathway in EGF-mediated hCG-beta production by JAr choriocarcinoma cells. Downregulation of protein kinase C activity by chronic exposure to the phorbol ester, phorbol 12,13-dibutyrate (PDB), produced a greater increase in hCG-beta secretion than did activation of protein kinase C activity by short-term exposure to PDB. Pretreatment with the protein kinase C inhibitors calphostin and chelerythrine also resulted in enhanced basal and EGF-stimulated hCG-beta production. Individual concentrations (5 nM EGF and 500 nM PDB) that maximally stimulated hCG production, were additive in combination. The additive effect of PDB on EGF-induced hCG-beta secretion was mediated in part by increased JAr cell EGF-receptor concentrations detected by Western blot and Scatchard analyses. The results suggest that EGF and PDB stimulate hCG production in JAr cells by different but interactive mechanisms. It is speculated that downregulation of protein kinase C stimulates basal and EGF-mediated hCG-beta production by uninhibiting other signalling pathways that regulate hCG-beta secretion in trophoblasts.

journal_name

Placenta

journal_title

Placenta

authors

Baker VL,Murai JT,Taylor RN

doi

10.1016/s0143-4004(98)91040-2

subject

Has Abstract

pub_date

1998-09-01 00:00:00

pages

475-82

issue

7

eissn

0143-4004

issn

1532-3102

pii

S0143-4004(98)91040-2

journal_volume

19

pub_type

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