Effects of transforming growth factor-beta on parathyroid hormone-related protein production and ribonucleic acid expression by a squamous carcinoma cell line in vitro.
The effects of human recombinant transforming growth factor (TGF)-beta 1 were determined on PTH-related protein (PTHrP) production and messenger RNA (mRNA) expression by a canine squamous carcinoma cell line (SCC 2/88) in vitro. TGF-beta increased PTHrP production in a dose- and time-dependent manner (P < 0.05) as measured by RIA, and the effects of TGF-beta treatment persisted up to 72 h after removal. TGF-beta increased PTHrP production by SCC 2/88 cells until cellular confluence, at which time there was no longer a significant increase compared to control. Actinomycin D inhibited the TGF-beta-mediated increase in PTHrP production, suggesting that TGF-beta acted in part by increasing gene transcription. SCC 2/88 cells also produced active TGF-beta as measured by a [3H]thymidine incorporation assay in mink lung epithelial cells. Exposure of SCC 2/88 cells to a neutralizing anti-TGF-beta monoclonal antibody decreased (up to 50%, P < 0.01) basal PTHrP production. TGF-beta increased PTHrP mRNA expression in a dose- and time-dependent manner as evaluated by northern blot analysis. Postconfluent SCC 2/88 cells expressed little mRNA for PTHrP, and there was only a minimal increase in PTHrP mRNA expression in postconfluent TGF-beta-treated cells. These results indicate that TGF-beta increased PTHrP production and mRNA expression in malignant keratinocytes and suggest that TGF-beta may be an important factor in the pathogenesis of humoral hypercalcemia of malignancy.
Merryman
J I
JI
Department of Veterinary Pathobiology, Ohio State University, Columbus 43210.
DeWille
J W
JW
Werkmeister
J R
JR
Capen
C C
CC
Rosol
T J
TJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002452:Cell Count; D003609:Dactinomycin / Q000494:pharmacology; D004285:Dogs; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D009062:Mouth Neoplasms / Q000378:metabolism; D044162:Parathyroid Hormone-Related Protein; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003609:Dactinomycin