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Lack of expression for the suppressor PML in human small cell lung carcinoma
Author(s) -
Zhang Ping,
Chin Wai,
Chow Louis T.C.,
Chan Andrew S.K.,
Yim Anthony P.C.,
Leung SingFai,
Mok Tony S.K.,
Chang KungSang,
Johnson Philip J.,
Chan John Y.H.
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(20000301)85:5<599::aid-ijc1>3.0.co;2-#
Subject(s) - suppressor , carcinoma , lung , biology , cancer research , small cell lung carcinoma , expression (computer science) , human lung , pathology , medicine , small cell carcinoma , oncology , cancer , genetics , computer science , programming language
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. Int. J. Cancer 85:599–605, 2000. © 2000 Wiley‐Liss, Inc.