Type

Journal Article

Authors

B J Harvey
G C O' Sullivan
C Taylor
D C Winter

Subjects

Microbiology

Topics
spectrometry fluorescence humans pharmacology cytology drug effects physiology dna replication colon tumor cells cultured cell membrane receptors estrogen mitogens estrogens

Mitogenic effects of oestrogen mediated by a non-genomic receptor in human colon. (2000)

Abstract Oestrogens are important mitogens in epithelial cancers, particularly where tumours express complementary receptors. While the traditional model of oestrogen action involves gene-directed (genomic) protein synthesis, it has been established that more rapid, non-genomic steroid hormone actions exist. This study investigated the hypothesis that oestrogen rapidly alters cell membrane activity, intracellular pH and nuclear kinetics in a mitogenic fashion. Crypts isolated from human distal colon and colorectal cancer cell lines were used as robust models. DNA replication and intracellular pH were measured by radiolabelled thymidine incorporation (12 h) and spectrofluorescence imaging respectively. Genomic protein synthesis, sodium-hydrogen exchanger (NHE) and protein kinase C (PKC) activity were inhibited with cycloheximide, ethylisopropylamiloride and chelerythrine chloride respectively. Oestrogen induced a rapid (less than 5 min) cellular alkalinization of crypts and cancer cells that was sensitive to NHE blockade (P < 0.01) or PKC inhibition (P < 0.01). Oestrogen increased thymidine incorporation by 44 per cent in crypts and by up to 38 per cent in cancer cells (P < 0.01), and this was similarly reduced by inhibiting the NHE (P < 0.01) or PKC (P < 0.05). Oestrogen rapidly activates cell membrane and nuclear kinetics by a non-genomic mechanism mediated by PKC but not gene-directed protein synthesis.
Collections Ireland -> University College Cork -> PubMed

Full list of authors on original publication

B J Harvey, G C O' Sullivan, C Taylor, D C Winter

Experts in our system

1
Brian J Harvey
Royal College of Surgeons in Ireland
Total Publications: 102
 
2
Cormac T. Taylor
University College Dublin
Total Publications: 110
 
3
Desmond C. Winter
University College Dublin
Total Publications: 53