Expression of transforming growth factor beta ligand and receptor messenger RNAs in lung cancer cell lines.
Specific cDNA probes for transforming growth factor beta s (TGF-beta s) 1, 2, and 3 and TGF-beta types I, II, and III receptors were used to study expression of the mRNAs of the different TGF-beta ligand and TGF-beta receptor isoforms in cultured non-small cell lung cancer (NSCLC) cells and small cell lung cancer (SCLC) cells. Expression of TGF-beta 1 mRNA was detected in both cell types using Northern blot hybridization, with the level of expression of this mRNA being higher in several NSCLC cell lines. In addition, expression of TGF-beta 2 and TGF-beta 3 mRNAs was also detected in NSCLC and SCLC cells but at levels that were lower than that of TGF-beta 1 mRNA. Besides expression of a 3.4-kilobase (kb) TGF-beta 3 transcript, a smaller 2.8-kb TGF-beta 3 transcript was detected in some NSCLC and SCLC cells. TGF-beta 1 and TGF-beta 2 proteins were detected in the conditioned media of NSCLC and SCLC cells, with the levels being higher in several NSCLC cells than in SCLC cells. Expression of TGF-beta types I and II receptor mRNAs was also detected in most NSCLC and SCLC cells, with expression of a 5.5-kb type I receptor mRNA being higher than that of a 5.5-kb type II receptor mRNA in both cell types. In contrast, a 6-kb TGF-beta type III receptor mRNA was detected in only some NSCLC cells and could not be detected in the SCLC cells examined. Also, there was an inverse relationship between the level of expression of the 5.5-kb TGF-beta type I receptor mRNA and that of the 6-kb TGF-beta type III receptor mRNA. Addition of TGF-beta 1 and TGF-beta 2 proteins resulted in an increase in the mRNAs for TGF-beta s 1 and 2 and an increase in the amount of TGF-beta 1 protein in some NSCLC cells, indicating that these cells are responsive to TGF-beta and its effects. At the same time, a differential change in expression of the 2.8- and 3.4-kb TGF-beta 3 transcripts was detected in some lung cancer cells following the addition of TGF-beta 1 and TGF-beta 2. Also, addition of TGF-beta 1 to NSCLC cells inhibited colony formation of some of these cells in soft agarose in a dose-dependent manner.(ABSTRACT TRUNCATED AT 400 WORDS)
Jakowlew
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SB
National Cancer Institute, Biomarkers and Prevention Research Branch, Rockville, Maryland 20850, USA.
Mathias
A
A
Chung
P
P
Moody
T W
TW
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D008024:Ligands; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta