Establishment and Maintenance of a Large Panel of Lung and Breast Cell Lines
The Minna and Gazdar labs have established more than 300 lung tumor cell lines during the past 20 years. We have characterized many of these cells by genome-wide expression profiling, whole-exon sequencing, in vitro colony formation, soft-agar assay, and tumorigenicity in immune-compromised mice. In addition, we have performed several drug and siRNA screenings to find critical vulnerabilities or targets for therapy. We have deposited many of these lung tumor cell lines in ATCC so that researchers around the world may have access to them.
We have created a large number of immortalized normal human bronchial epithelial cell lines (HBECs) and small airway epithelial lines (HSAECs) by over-expressing CDK4 and hTERT genes. HBECs and HSAECs have many features of normal cells: their growth is contact inhibited and anchorage-dependent and they don’t form tumors in immune-deficient mice. These features make HBECs and HSAECs ideal models to study tumor transformation originating in the central and peripheral lung respectively.
We have stably introduced oncogenes (mutated KRAS, EGFR, c-MYC , etc.) and knocked down tumor suppressor genes (p53, LKB1, etc.) to study stepwise lung tumor transformation. We showed the combination of over-expression of oncogenes and knockdown of tumor suppressor genes can transform HBECs and HSAECs to full malignancy. These isogenic cell lines are powerful tools to identify driver mutations in lung cancer. They are also used extensively in all areas of research in our lab.
We are generating several new lung cancer cell lines together with HBECs/HSAECs from the same individuals to compare the genetic and functional differences between the tumor and normal cells. These paired cells are ideal reagents to screen drugs that inhibit tumor cell growth while having minimal effect on normal cells. (We are generating several new lung cancer cell lines together with HBECs/HSAECs from the same individuals (see banner picture 1 on home page) to compare the genetic and functional differences between the tumor and normal cells. These paired cells are ideal reagents to screen drugs that inhibit tumor cell growth while having minimal effect on normal cells.)
We are developing conditionally reprogrammed tumor and normal cells (CRCs) using a ROCK inhibitor and irradiated mouse feeder layers. This technology has allowed the growth of nearly all lung cancers and normal lung epithelial cells from very small biopsy specimens.
We have generated several patient-derived xenograft (PDX) models using tumor tissue taken directly from patients and transplanted into immune-deficient mice. These are ideal models for in vivo drug screening and validation studies.