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Alterations of PTEN/MMAC1, a candidate tumor suppressor gene, and its homologue, PTH2, in small cell lung cancer cell lines.
- Source :
-
Oncogene [Oncogene] 1998 Jan 08; Vol. 16 (1), pp. 89-93. - Publication Year :
- 1998
-
Abstract
- Loss of heterozygosity (LOH) at chromosome 10q23-q25 is frequent in small cell lung cancer (SCLC), indicating the presence of putative tumor suppressor genes. PTEN/ MMAC1, a newly cloned candidate tumor suppressor gene at 10q23, was mutated in multiple human cancers. We investigated whether mutations of PTEN/MMAC1 play an important role in SCLC tumorigenesis. We examined 16 SCLC cell lines for PTEN/MMAC1 mRNA expression by reverse-transcriptase polymerase chain reaction (RT-PCR) and potential mutations by sequencing analysis of the PTEN/MMAC1 coding region. No mutation was observed in PTEN/MMAC1 cDNAs in 15 cell lines expressing PTEN/MMAC1. One SCLC cell line, DMS79, did not have detectable PTEN/ MMAC1 expression. Importantly, we identified a novel homologue of PTEN/MMAC1, termed PTH2, localized to chromosome 9p21-q13 and containing only ten amino acid substitutions compared with the PTEN/MMAC1 coding region. However, because the putative initiation codon for PTEN/MMAC1 gene was changed to arginine in PTH2, the translational initiation site of PTH2 is very likely to differ from that of the PTEN/MMAC1. PTH2 was expressed in two normal lung tissues and two normal colon tissues, but in only four of 16 SCLC cell lines. A missense mutation in PTH2 was identified in a SCLC cell line that did not express PTEN/MMAC1 mRNA. Our data suggest that inactivation of PTEN/ MMAC1 is a rare event in SCLC tumorigenesis. However, the PTEN/MMAC1 homologue PTH2 may play a role in SCLC tumorigenesis.
- Subjects :
- Amino Acid Sequence
Base Sequence
Carcinoma, Small Cell pathology
Chromosome Mapping
Chromosomes, Human, Pair 9
DNA, Complementary
Humans
Lung Neoplasms pathology
Molecular Sequence Data
PTEN Phosphohydrolase
Polymerase Chain Reaction
Sequence Homology, Amino Acid
Tumor Cells, Cultured
Carcinoma, Small Cell genetics
Genes, Tumor Suppressor
Lung Neoplasms genetics
Phosphoric Monoester Hydrolases
Protein Tyrosine Phosphatases genetics
Proteins genetics
Tumor Suppressor Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 9467947
- Full Text :
- https://doi.org/10.1038/sj.onc.1201512