Effect of Nma on growth inhibition by TGF-betaa in human gastric carcinoma cell lines.
Non-metastatic gene A (nma) has a homologue DNA sequence to a gene of bone morphogenetic proteins and activin membrane-bound inhibitor (BAMBI), which negatively regulates TGF-beta signaling. In this study, we analyzed the functional homology between Nma and BAMBI in human gastric carcinoma cell lines. Various levels of nma mRNA expression were detected by the RT-PCR technique in all human gastric carcinoma cell lines. Then, Nma antisense and sense S-oligodeoxynucleotide (ODN) were used to analyze the response of TGF-beta to cell growth and invasion gastric carcinoma cell lines. The cell growth was inhibited by TGF-beta in Nma antisense S-ODN treatment gastric carcinoma cell lines, MKN28, MKN1, MKN74 and TMK1. TGF-beta reduced cell growth and invasive activity of MKN28 treated with Nma antisense S-ODN in a dose and time-dependent manner. Furthermore, lysates of Nma sense or antisense S-ODN treated MKN28 cells were immunoprecipitated with anti-TGFbetaR-I or anti-TGFbetaR-II antibody. The 29 kDa signal considered as Nma appeared in sense S-ODN treated MKN28 cells immunoprecipitated with anti-TGFbetaR-I. These results indicate that Nma negatively regulates TGF-beta signaling, consequently playing an important role as one of the escape mechanisms from TGF-beta-mediated growth control similarly to BAMBI, and induce cell growth and invasion in human gastric carcinoma cell lines.
Sasaki
Takamitsu
T
Department of Oncological Pathology, Nara Medical University Cancer Center, Kashihara, Nara 634-8521, Japan.
Sasahira
Tomonori
T
Shimura
Hideo
H
Ikeda
Seiyo
S
Kuniyasu
Hiroki
H
D030201:Activin Receptors, Type I / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000502:physiology*; D009361:Neoplasm Invasiveness / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D013873:Thionucleotides / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
C485671:BAMBI protein, human; D008565:Membrane Proteins; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D013873:Thionucleotides; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000077294:Receptor, Transforming Growth Factor-beta Type II