Start Your Search
MO04 - Lung Cancer Biology I (ID 86)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Biology
- Presentations: 1
MO04.07 - Chronic lung injury by constitutive expression of AID leads to focal alveolar regeneration and cancer (ID 116)
16:15 - 17:45 | Author(s): J. Kitamura
Activation-induced cytidine deaminase, AID, is an enzyme required for somatic hypermutation and class-switch recombination which diversify immunoglobulin genes and causes DNA mutations and strand breaks. Uncontrolled expression of AID is cytotoxic. AID transgenic mice invariably develop lung lesions morphologically similar to human atypical adenomatous hyperplasia (AAH), which can be a precursor of bronchioloalveolar carcinoma. About 10 % of these mice develop visible lung tumor including adenocarcinoma. However, the relationship between this mouse AAH-like lesion (MALL) and lung cancer is unclear. In the present study, we examined MALLs to elucidate their characteristics and involvement in lung cancer.
p53, KRAS, and EGFR mutation status in each laser-microdissected MALL were analyzed. The expression of airway epithelial cell markers and lung alveolar regeneration markers in MALLs were investigated by immunohistochemistry. Apoptosis assay were performed in murine lungs. For cell proliferation assay, AID Tg mice were received a daily intraperitoneal injection of 1 mg 5-ethynyl-2’-deoxyuridine (EdU) for 7 days. Then, mice were studied 1 day (day 1) or 3 weeks (day 20) after the last injection.
We found mutations of p53 in 10.5% of MALLs (4/38), but no mutations of KRAS and EGFR. In immunohistochemistry, MALLs were partially positive for SP-C (lung alveolar type II cell-specific marker), but negative for CC-10 (clara cell-specific marker) and podoplanin (lung alveolar type I cell-specific marker). Frequency of apoptotic cells among lung alveolar wall cells was significantly higher in AID transgenic mice than in wild type mice. Moreover, frequency of Edu-positive MALL decreased significantly at day 20 compared to that at day 1. The expressions of p63, cytokeratin 5/14, and E-cadherin/Lgr6, the recently described markers of lung alveolar regeneration, were observed in MALLs.
Based on these observations, we speculate that MALL is a regenerating tissue compensating for alveolar epithelial cell loss caused by AID-induced genotoxic stress. AID expression in such regenerating tissue should predispose cells to malignant transformation by its mutagenic activity. AID transgenic mice could be a mouse model that may provide the link between lung regeneration after injury and the development of lung cancer.
Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.