Abstract
Developing lung cancer in mouse models that display similarities of both phenotype and genotype will undoubtedly provide further and better insights into lung tumor biology. Moreover, a high degree of pathophysiological similarity between lung tumors from mouse models and their human counterparts will make it possible to use these mouse models for preclinical tests. Ovine pulmonary adenocarcinomas (OPAs) present the same symptoms as adenocarcinomas in humans and are caused by a betaretrovirus. OPAs have served as an exquisite model of carcinogenesis for human lung adenocarcinomas. In this study, we characterized the histopathology and transcriptome profiles of a jaagsiekte sheep retrovirus (JSRV)-envelope protein (Env) transgenic mouse model with spontaneous lung tumors, and associations of the transcriptome profiles with tumor invasion/metastasis, especially the phenomenon of the epithelial-mesenchymal transition (EMT). Genetic information obtained from an expression array was analyzed using an ingenuity pathways analysis (IPA) and human disease database (MalaCards). By careful examination, several novel EMT-related genes were identified from tumor cells using RT-qPCR, and these genes also scored high in MalaCards. We concluded that the JSRV-Env mouse model could serve as a spontaneous lung adenocarcinoma model with a metastatic phenotype, which will benefit the study of early-onset and progression of lung adenocarcinoma. In addition, it can also be a valuable tool for biomarkers and drug screening, which will be helpful in developing intervention therapies.
Highlights
Lung cancer is one of the most common forms of cancer which remains the leading cause of cancer-related deaths worldwide among men and women
non-small-cell lung cancer (NSCLC) are further divided into squamous cell carcinomas (SCCs), pulmonary adenocarcinomas (ADCs), and large-cell carcinomas
adenomatous hyperplasia (AAH) featured uniform nuclei, while the nuclear pattern became pleomorphic in adenocarcinoma in situ (AIS) (Fig 1b and 1c)
Summary
Lung cancer is one of the most common forms of cancer which remains the leading cause of cancer-related deaths worldwide among men and women. Lung cancers are composed of two major histological types: small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC). In 2004, the World Health Organization (WHO) classification recognized a particular subtype, bronchioloalveolar carcinoma (BAC), which later was renamed adenocarcinoma in situ (AIS), for its non-invasive features and excellent prognosis [1,2]. These noninvasive lung lesions are more commonly found in non-smokers, women, and Asian populations [3,4]. AIS is considered the probable cancerous lesion of human lung ADC and develops from its precursor, atypical adenomatous hyperplasia (AAH) [5]. A recent study showed that genetic alterations involve in the progression of AAH to AIS [7]
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