Immortalized Human Lung Epithelial Cells

BTC is Sufficient to Cause Cellular Transformation of NIH3T3 Cells and Promote Anchorage-Independent Growth of Immortalized Human Lung Epithelial Cells

Oncogenic EGFR mutations are found in 15-20% of lung adenocarcinoma (LUAD) cases, but the mechanisms driving tumor development are not fully understood. Chava et al. identifies betacellulin (BTC) as a gene upregulated by oncogenic EGFR and investigates its role in LUAD.

Given that BTC expression relies on EGFR-MAPK-ERK signaling, they explored if overexpressing BTC could transform NIH3T3 cells. They introduced either an empty vector or BTC into these cells and tested their ability to grow without anchorage in soft agar and form tumors in mice. Overexpressing BTC led to larger colonies in soft agar (Fig. 1A and B), showing it promotes anchorage-independent growth. When injected into mice, NIH3T3 cells with BTC formed tumors, while those with the empty vector mostly did not (Fig. 1C). This confirms that overexpressing BTC transforms NIH3T3 cells. We also tested BTC overexpression in human airway epithelial cells (HSAEC1-KT). These cells, modified with hTERT and Cdk4, gained a growth advantage with BTC under anchorage-independent conditions (Fig. 1D). However, they didn't form tumors in mice, highlighting that human cells need multiple genetic changes for full transformation. Overall, overexpressing BTC can transform mouse cells and boost the growth of immortalized human lung epithelial cells without anchorage.