Expression of latent TGF-beta binding protein LTBP-1 is hormonally regulated in normal and transformed human lung fibroblasts.
Latent transforming growth factor-beta binding proteins (LTBPs), participate in the secretion, targeting and activation of transforming growth factor-beta (TGF-beta) isoforms. Besides the regulation of the bioavailability of TGF-betas, LTBPs are secreted as free forms and they associate with extracellular fibrillar structures. The current study was carried out to understand hormonal regulation of LTBP-1 expression in normal and SV-40 virus transformed human lung fibroblasts. LTBP-1 protein and mRNA expression were analysed by immunoblotting and Northern hybridisation. Basal expression levels of LTBP-1 were significantly reduced in the transformed cells. Retinoic acid (RA) as well as 9-cis-RA increased LTBP-1 expression in both cell lines, probably through post-transcriptional mechanisms. Dexamethasone induced LTBP-1 protein and mRNA levels in both cell lines. The effect was much more prominent in transformed cells and involved both transcriptional and post-transcriptional events. Vitamin D, estradiol and tamoxifen had only negligible effects on LTBP-1 expression. TGF-beta1 increased its own expression as well as LTBP-1 levels in both cell lines, but the response was clearly of lower magnitude in transformed cells. This may reflect insensitivity to TGF-beta1, which is a common feature for malignant cells. Our results indicate that LTBP-1 expression is under the regulation of RA and corticoids in lung fibroblasts. The responses to these hormonal modulators may either be lost or enhanced in transformed cells, which likely contributes to malignant growth.
Weikkolainen
Krista
K
Department of Virology, Haartman Institute and Biomedicum Helsinki, University of Helsinki and Helsinki University Hospital, FIN-00014 Helsinki, Finland.
Keski-Oja
Jorma
J
Koli
Katri
K
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism*; D002461:Cell Line, Transformed; D016895:Culture Media, Serum-Free; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D008168:Lung / Q000378:metabolism*; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; D047908:Intracellular Signaling Peptides and Proteins; C509032:LTBP1 protein, human; D053779:Latent TGF-beta Binding Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003609:Dactinomycin; D014212:Tretinoin; D003907:Dexamethasone; D003513:Cycloheximide