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Lack of expression for the suppressor PML in human small cell lung carcinoma
1Department of Surgery, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China.
Abstract:
The promyelocytic leukemia (PML) gene, which encodes a transformation and growth suppressor, was first identified at the chromosomal translocation break point t(15;17) in acute promyelocytic leukemia (PML). To determine if the PML gene might be involved in other neoplasias such as lung cancer, PML expression was analyzed by immunohistochemical staining and in situ hybridization. Considerable PML protein expression in the PML-oncogenic domain (POD) structure was found in adenocarcinomas (ADC) and squamous cell carcinomas (SCC) of the lung, but was almost completely absent in all the small cell lung carcinomas (SCLC) examined. In situ hybridization showed that both mRNA and DNA of PML were present in SCLC and in normal lung, suggesting that the decreased protein expression was due to either a defect in translation or protein instability, rather than the consequence of decreased transcription or gene deletion. Double staining showed that PML expression was inversely correlated with the proliferation marker Ki-67 and positively correlated with levels of apoptotic cells in these tumors. To determine if the precursor cells of SCLC, the neuroendocrine-producing cells, express PML, double labeling was performed with PML and chromogranin A, a bio-marker for neuroendocrine cells. Neuroendocrine cells from normal tissues were found to be PML positive, indicating that the lack of PML protein in SCLC is associated with the tumorigenic phenotype and is not the result of cell-lineage specificity. Thus, the decreased PML expression may play an important role in SCLC development.
Insights
The promyelocytic leukemia (PML) gene, a tumor suppressor, is highly expressed in lung adenocarcinomas and squamous cell carcinomas but absent in small cell lung carcinomas. This decreased PML expression may drive small cell lung cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The promyelocytic leukemia (PML) gene acts as a tumor suppressor and was initially identified in acute promyelocytic leukemia.
- Its potential role in other cancers, like lung cancer, requires investigation.
Purpose of the Study:
- To investigate the expression patterns of the PML gene in various types of lung cancer.
- To determine the correlation between PML expression and tumor characteristics, including proliferation and apoptosis.
Main Methods:
- Immunohistochemical staining and in situ hybridization were used to analyze PML expression in lung cancer tissues.
- Double staining techniques were employed to assess PML expression alongside proliferation markers (Ki-67) and neuroendocrine cell markers (chromogranin A).
Main Results:
- Significant PML protein expression was observed in lung adenocarcinomas (ADC) and squamous cell carcinomas (SCC).
- PML expression was notably absent in small cell lung carcinomas (SCLC).
- Decreased PML protein in SCLC is likely due to translational or protein stability defects, not gene deletion or reduced transcription.
Conclusions:
- PML expression is inversely correlated with proliferation (Ki-67) and positively correlated with apoptosis in lung tumors.
- Normal neuroendocrine cells express PML, indicating that its absence in SCLC is linked to tumorigenesis, not cell-lineage specificity.
- Reduced PML expression may be a critical factor in the development of small cell lung cancer.