GSE67934
Gene expression changes associated with chemo-resistance in small cell lung cancer
Small cell lung cancer (SCLC) is a neuroendocrine lung tumor that responds well to chemotherapy but inevitably develops resistance, with limited second-line treatments available. Using a transcriptomic approach, we show that chemo-resistant SCLC loses neuronal fate and adopts a mid/hindgut fate that highly mimics events in embryonic endoderm development. In response to chemotherapy, SCLC cells gain expression of the intestinal regulator Caudal type homeobox 2 (Cdx2), which promotes an intestinal gene expression program Overall design: Mouse cell line 3151T1, derived from SCLC tumors from conditional Rbfl/fl;p53fl/fl mice infected with adenoviral Cre, were repeatedly treated with EC20 doses of vehicle-control (P), cisplatin (CR), etoposide (ER) or both (ECR) until they became resistant (5-20X). RNA was extracted from cells in duplicate and subjected to paired end RNA sequencing.