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Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines
- Source :
- British Journal of Cancer
- Publication Year :
- 1999
-
Abstract
- Transforming growth factor β (TGF-β) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-β due to lack of type II receptor (RII) has been described in some cancer types including small cell lung cancer (SCLC). The purpose of this study was to examine the cause of absent RII expression in SCLC cell lines. Northern blot analysis showed that RII RNA expression was very weak in 16 of 21 cell lines. To investigate if the absence of RII transcript was due to mutations, we screened the poly-A tract for mutations, but no mutations were detected. Additional screening for mutations of the RII gene revealed a GG to TT base substitution in one cell line, which did not express RII. This mutation generates a stop codon resulting in predicted synthesis of a truncated RII of 219 amino acids. The nature of the mutation, which has not previously been observed in RII, has been linked to exposure to benzo[a]-pyrene, a component of cigarette smoke. Since RII has been mapped to chromosome 3p22 and nearby loci are often hypermethylated in SCLC, it was examined whether the lack of RII expression was due to hypermethylation. Southern blot analysis of the RII promoter did not show altered methylation patterns. The restriction endonuclease pattern of the RII gene was altered in two SCLC cell lines when digested with Sma 1. However, treatment with 5-aza-2′-deoxycytidine did not induce expression of RII mRNA. Our results indicate that in SCLC lack of RII mRNA is not commonly due to mutations and inactivation of RII transcription was not due to hypermethylation of the RII promoter or gene. Thus, these data show that in most cases of the SCLC cell lines, the RII gene and promoter is intact in spite of absent RII expression. However, the nature of the mutation found could suggest that it was caused by cigarette smoking. © 1999 Cancer Research Campaign
- Subjects :
- Cancer Research
endocrine system
Lung Neoplasms
type II receptor
chemical and pharmacologic phenomena
cell lines
Biology
Protein Serine-Threonine Kinases
Methylation
Transcription (biology)
Tumor Cells, Cultured
Humans
Northern blot
RNA, Messenger
Carcinoma, Small Cell
Receptor
transforming growth factor β
Gene
Polymorphism, Single-Stranded Conformational
Messenger RNA
Receptor, Transforming Growth Factor-beta Type II
hemic and immune systems
Regular Article
respiratory system
Blotting, Northern
biological factors
Blot
Blotting, Southern
Oncology
Mutagenesis
DNA methylation
Cancer research
small cell lung cancer
mutation
transcription
Receptors, Transforming Growth Factor beta
Transforming growth factor
Subjects
Details
- ISSN :
- 00070920
- Volume :
- 79
- Issue :
- 7-8
- Database :
- OpenAIRE
- Journal :
- British journal of cancer
- Accession number :
- edsair.doi.dedup.....3219483fbc8664b2faf7f3024bde3ebc