Abstract 4716: Glutathione S transferase omega 2 (GSTO2) is a novel tumor suppressor gene of human lung squamous cell carcinoma

Lung cancer is one of the most common malignant diseases and the leading cause of cancer death globally. The clinical, pathologic, and genomic characteristics of lung cancer are very diverse. Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancers and can be histologically class...

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Veröffentlicht in:Cancer research (Chicago, Ill.) Ill.), 2020-08, Vol.80 (16_Supplement), p.4716-4716
Hauptverfasser: Sumiya, Ryusuke, Terayama, Masayoshi, Hagiwara, Teruki, Sekihara, Keigo, Nagasaka, Satoshi, Yamada, Kazuhiko, Kokudo, Norihiro, Kawamura, Yuki I.
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Sprache:eng
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Zusammenfassung:Lung cancer is one of the most common malignant diseases and the leading cause of cancer death globally. The clinical, pathologic, and genomic characteristics of lung cancer are very diverse. Non-small cell lung cancer (NSCLC) is the most frequent type of lung cancers and can be histologically classified into lung adenocarcinoma and squamous cell carcinoma (SCC). Lung adenocarcinoma is generally located in alveolar or endobronchial, whereas LSCC frequently arises in bronchi and bronchiole. Molecular-targeted drugs have been developed for lung adenocarcinoma; however, there is currently no definite clinical implication for lung SCC (LSCC). Therefore, to increase the cure and survival rates of lung cancers, developing type-specific diagnostic/prognostic markers and treatment methods might improve this situation. One of the major risk factors of LSCC is smoking, which causes aberrant DNA methylation, abnormal gene expression, and eventually malignant transformation. We previously identified glutathione S-transferase omega 2 (GSTO2) as one of DNA methylation target genes in esophageal SCC (Otsubo T, Oncotarget, 8, 84434-84448, 2017). We reported that GSTO2 was exclusively expressed in nethermost basal cells which are believed to function as stem cells in normal esophageal mucosa. Furthermore, GSTO2 overexpression in esophageal SCC cells significantly inhibited cell growth in vitro and in vivo. (Terayama M, Carcinogenesis, in press). In present study, we investigated the expression and function of GSTO2 in normal lung and LSCC. In normal bronchi and bronchiole containing a variety of epithelial cell populations such as ciliated cells, non-ciliated, columnar Clara cells, and basal cells, GSTO2 was expressed in cytokeratin 5/6-positive airway basal cells. In contrast, all 94 LSCC specimens examined in this study showed no GSTO2 expression. To clarify the significance of GSTO2 silencing LSCC, we restored GSTO2 expression in LK-2 LSCC cells. Overexpression of GSTO2 significantly inhibited cell growth compared with the mock-transfected LK-2 cells. In colony formation assay, GSTO2-transfected cells failed to form colonies, whereas mock-transfected cells formed colonies efficiently. When human LSCC cell lines (LK-2 and EBC-1) were treated with 5-aza-2'-deoxycytidine (5-aza-dC), a DNA-methyltransferase inhibitor, the GSTO2 transcription was induced, indicating that aberrant hypermethylation of the GSTO2 in LSCC was likely the cause of the downregulated expression. Cons
ISSN:0008-5472
1538-7445
DOI:10.1158/1538-7445.AM2020-4716