Transforming growth factor beta may act as an autocrine-survival-promoting factor for transformed trophoblasts.
Using five trophoblast cell lines of different differentiation status, we have shown that trophoblasts could constitutively release the transforming growth factor beta-1 (TGFbeta1), but not TGFbeta2. Treatment of the human tumorigenic, TL, and BeWo cells with a differentiating agent and a potent protein kinase C activator--the tumor-promoting agent--or the JEG-3 cells with cholera toxin--a potent cyclic adenosine 3':5'monophosphate (cAMP) inducer--or its analogue 8-bromo-cAMP, potentiates TGFbeta production, but the two signaling pathways appear to be mutually exclusive. Surprisingly, the JAR tell line failed to respond to either type of TGFbeta activator. Based on reverse transcriptase (RT)-polymerase chain reaction (PCR), it was found that only the JAR cell line expressed messenger ribonucleic acid for decorin, a natural inhibitor of TGFbeta, and none of the cell lines had detectable protein expression as determined by immunocytochemical studies. The tell number in cultures with decorin was invariably lesser than in those without decorin under serum-free conditions for all the cell lines tested. These results suggest that TGFbeta may act as an autocrine-survival factor for transformed trophoblasts by allowing the cells to survive longer under a microenvironment which is not favorable for growth. Lastly, our results indicate that decorin, acting in a paracrine manner, may also play an important negative regulatory role in the development of transformed trophoblasts by sequestering TGFbeta, thereby preventing its action.
Ho
C K
CK
Department of Medical Research & Education, Veterans General Hospital--Taipei and Institute of Traditional Medicine, National Yang-Ming University, Taiwan, ROC. cclin3@vghtpe.gov.tw
Peng
H J
HJ
Wang
S Y
SY
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000502:physiology*; D002772:Cholera Toxin / Q000494:pharmacology; D017931:DNA Primers; D058575:Decorin; D020536:Enzyme Activators / Q000494:pharmacology; D016326:Extracellular Matrix Proteins; D011493:Protein Kinase C / Q000378:metabolism; D011509:Proteoglycans / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000502:physiology*; D014327:Trophoblasts / Q000166:cytology*
C546878:DCN protein, human; D017931:DNA Primers; D058575:Decorin; D020536:Enzyme Activators; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002772:Cholera Toxin; D011493:Protein Kinase C