| Abstract: | Lung cancer has been the major cause of Taiwanese cancer death since 1982 [1, 2]. There are about 5,000 due to lung cancer as well as 6,000 new cases of lung cancer per year [1, 2]. By contrast, the 5 year survival rates for lung cancers are significant higher in early stages (Stage I) than advanced stage (Stage IV) in Taiwan [3]. Thus, early diagnosis is very important for improving the prognosis of lung cancers. In other words, a good detection test for early lung cancers is needed. AhR signaling pathway is a major pathway for xenobiotic and drug metabolism in human. AhR is a basic helix-loop-helix (bHLH) protein belonging to the Per-Arnt-Sim (PAS) family of transcription factors.While ligand binding, AhR sheds the chaperon proteins and translocates to the nucleus, where it forms a heterodimer with the AhR nuclear translocator (ARNT).This heterodimer binds to the xenobiotic response element (XRE) of human CYP1A1, CYP1A2, and CYP1B1 genes activating transcription [4]. AhR ligands include polycyclic aromatic hydrocarbons (PAHs, BaP as representative), dioxin (2,3,7,8-Tetrachlorodibenzo-p-dioxin, TCDD, as representative) and cigarette smoke, which are carcinogenic for lung cancers [5-7]. In human, epidemiological evidence showed that the carcinogenic risk associated with TCDD exposure was increased for all cancers combined including non-Hodgkin's lymphoma, soft tissue sarcoma, rectal cancer and lung cancer [8]. Accordingly, AhR signaling pathway might involve the human carcinogenesis. Lung cancers are clinically categorized into small cell cancers and non-small cell lung cancers. Squamous cell carcinoma and adenocarcinoma are two major types of histology. Concerning the tumorigenesis of human lung cancers, squamous cell carcinoma and adenocarcinoma are different. The progression of squamous cell carcinoma is recognized through squamous metaplasia, dysplasia and carcinoma in situ in the bronchi. Adenocarcinomas locate mostly in lung periphery. Peripheral lung adenocarcinomas are considered to be derived from type II pneumocytes or Clara cells, based on the phenotype of neoplastic cells [9, 10]. Kitamura and co-workers [10] reported that atypical adenomatous hyperplasia (AAH), as a precancerous lesion, was thought to be the adenoma in a putative "adenoma-carcinoma" sequence, and lead to the development of bronchioloalveolar carcinoma (BAC) and invasive adenocarcinoma [11]. Thus, AAH-BAC-adenocarcinoma may be a progression model of peripheral adenocarcinomas. This progression model may be used to understand the genetic alterations in multistage development of peripheral lung adenocarcinoma. |
