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[Loss and inactivation of PTEN/MMAC1/TEP1 gene in lung cancer]
1Department of Pathology, Peking Union Medical Hospital, Peking Union Medical College, Chinese Academy of Sciences, Beijing 100730 China.
Objective:
The recently identified PTEN/MMAC1/TEP1 gene is the first tumor suppressor encoding a phosphatase, which mutated in multiple tumors. Our research aims to detect loss of heterozygosity and inactivation of PTEN in lung cancer.
Methods:
24 lung cancer fresh samples paired with normal tissue, 18 archival paraffin-embedded sections of small cell lung cancer (SCLC) were included. For 24 fresh samples, PCR-LOH was used to detect Loss of heterozygosity (LOH) in or near PTEN loci. In situ hybridization, Western blot and or immunohistochemistry were proceeded for mRNA and protein expression of PTEN in lung cancer samples. Southern, Northern and Western blot were done to exam PTEN abnormality in one NSCLC and three SCLC cell lines.
Results:
Among these 24 fresh samples PTEN LOH was detected in 11 out of 24 cases (45.8%) and 6 cases had no PTEN mRNA and protein expression. Results in situ hybridization were in conformity with that of immunohistochemistry/Western blot in our research. No protein expression was detected in 8/18 (44%) archival paraffin cases of SCLC. Southern, Northern and Western blot confirmed homozygous deletion in one SCLC cell line.
Conclusion:
Lung cancers had LOH and inactivation of PTEN.
Insights
PTEN gene loss and inactivation are frequent in lung cancer, affecting nearly half of fresh samples and many small cell lung cancer cases. This suggests PTEN is a critical tumor suppressor in lung tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The PTEN gene, encoding a phosphatase, is a known tumor suppressor frequently mutated in various cancers.
- Understanding PTEN alterations in lung cancer is crucial for identifying potential therapeutic targets.
Purpose of the Study:
- To investigate the frequency of Loss of Heterozygosity (LOH) and inactivation of the PTEN gene in lung cancer.
- To assess PTEN mRNA and protein expression in lung cancer tissues and cell lines.
Main Methods:
- Analysis of 24 fresh lung cancer samples and 18 archival small cell lung cancer (SCLC) samples.
- Polymerase Chain Reaction (PCR)-based LOH detection for PTEN loci.
- In situ hybridization, Western blot, and immunohistochemistry for PTEN expression analysis.
- Southern, Northern, and Western blot analyses on lung cancer cell lines.
Main Results:
- PTEN LOH was observed in 11 of 24 (45.8%) fresh lung cancer samples.
- Absence of PTEN mRNA and protein expression was detected in 6 fresh samples and 8 of 18 (44%) archival SCLC cases.
- Homozygous deletion of PTEN was confirmed in one SCLC cell line.
Conclusions:
- Loss of heterozygosity and inactivation of the PTEN gene are common events in lung cancer.
- These findings highlight PTEN's role as a tumor suppressor in lung tumorigenesis.
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