Expression of neuregulin 4 splice variants in normal human tissues and prostate cancer and their effects on cell motility.
The neuregulin 4 gene encodes at least five different variants (designated A1, A2, B1, B2 and B3) produced as a result of alternative splicing. We have determined their sites of expression in normal human adult tissues using isoform-specific antibodies. Their expression is cell type specific and differs in subcellular location suggesting that they may have varied functions in these contexts. We have shown in a panel of prostate cancers that each form is present to differing degrees, and that principal component analysis indicates that there are three patterns of expression. Some isoforms were positively correlated with high prostate-specific antigen levels and others were inversely associated with Gleason score. Synthetic, refolded A forms promoted lamellipodia and filopodia formation in cells expressing the ErbB4 (CTa) receptor and stimulated cell motility in wound healing assays. The data suggest that the different forms have varied sites of expression and function, and this includes effects on cell architecture and motility.
Cancer Biology Laboratory, School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Nandini V L
NV
Hayes
Edith
E
Blackburn
Mary M
MM
Boyle
Graham A
GA
Russell
Teresa M
TM
Frost
Byron J T
BJ
Morgan
William J
WJ
Gullick
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017398:Alternative Splicing; D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000502:physiology*; D002522:Chlorocebus aethiops; D006801:Humans; D008297:Male; D051379:Mice; D041681:NIH 3T3 Cells; D020880:Neuregulins / Q000096:biosynthesis* / Q000235:genetics; D025341:Principal Component Analysis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020033:Protein Isoforms; D014162:Transfection
D020880:Neuregulins; D020033:Protein Isoforms; C467747:neuregulin-4; D017430:Prostate-Specific Antigen