PHOSPHATASE INHIBITORS, GAP JUNCTIONAL INTERCELLULAR COMMUNICATION AND [I-125] EGF BINDING IN HAMSTER FIBROBLASTS

Citation
T. Husoy et al., PHOSPHATASE INHIBITORS, GAP JUNCTIONAL INTERCELLULAR COMMUNICATION AND [I-125] EGF BINDING IN HAMSTER FIBROBLASTS, Carcinogenesis, 14(11), 1993, pp. 2257-2265
Citations number
68
Categorie Soggetti
Oncology
Journal title
ISSN journal
01433334
Volume
14
Issue
11
Year of publication
1993
Pages
2257 - 2265
Database
ISI
SICI code
0143-3334(1993)14:11<2257:PIGJIC>2.0.ZU;2-P
Abstract
A number of phosphatase inhibitors (okadaic acid, calyculin A, alumini um fluoride, sodium molybdate, sodium orthovanadate, pervanadate and v anadyl sulphate) were investigated for their effects on gap junctional intercellular communication (GJIC) and [I-125]-epidermal growth facto r (EGF) binding in early passage Syrian hamster embryo cells (mainly f ibroblast-like cells) and in V79 Chinese hamster lung fibroblasts. Onl y pervanadate decreased GJIC significantly. After the initial pervanad ate-induced decrease the GJIC recovered rapidly. Only pervanadate was able to change the band pattern of the pp junction protein connexin43 (cx43) in Western blots. Together this may indicate either that there is a low turnover of phosphate groups in cx43 under basal conditions o r that the putative phosphatases are not sensitive to most of the phos phatase inhibitors applied. In contrast, pervanadate, orthovanadate an d molybdate decreased [I-125]-EGF binding. 12-O-Tetradecanoylphorbol-1 3-acetate (TPA) is able to induce the phosphorylation of both cx43 and the EGF receptor, concomitantly with a decrease in GJIC and [I-125]-E GF binding. These effects are reversible after removal of TPA. It coul d be imagined that other phosphatases would act on cx43 and the EGF re ceptor after the forced phosphorylation of the two molecules. Thus TPA was used to downregulate GJIC and [I-125]-EGF binding and phosphatase inhibitors were applied in the upregulation phase. Only pervanadate a ffected the upregulation of GJIC, and pervanadate, orthovanadate and m olybdate affected the upregulation of [I-125]-EGF binding. Thus it is not an identical complement of phosphatases that act on cx43 and the E GF receptor. All the downregulating agents are assumed to be phosphoty rosine phosphatase inhibitors.