Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255

Sean Tracy, Toru Mukohara, Mark Hansen, Matthew Meyerson, Bruce E. Johnson, Pasi A. Jänne

Research output: Contribution to journalArticlepeer-review

329 Scopus citations


Somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) have recently been described in patients with non-small-cell lung cancer (NSCLC) who achieve radiographic regressions to the EGFR inhibitor gefitinib. One of these mutations, L858R (Leu→Arg), is also found in NSCLC cell line H3255, which is very sensitive to gefitinib treatment. We characterized nine NSCLC cell lines (three isolated from patients with bronchioloalveolar carcinoma and six isolated from patients with adenocarcinoma) for their in vitro sensitivity to gefitinib. Of these, only H3255 (EGFR L858R) and H1666 (EGFRWT) are sensitive to gefitinib with IC50 values of 40 nmol/L and 2 μmol/L, respectively. We examined the effects of gefitinib on H3255 and cell lines containing wild-type EGFR that are either sensitive (H1666) or resistant (A549 and H441) to gefitinib exposure in vitro. Gefitinib treatment (1 μmol/L) leads to significant apoptosis accompanied by increased poly(ADP-ribose) polymerase cleavage only in the H3255 cell line, leads to G1-S arrest in H1666, and has no effects in the A549 and H441 cell lines. Although EGFR and AKT are constitutively phosphorylated in H3255, H1666, and H441 cell lines, AKT is completely inhibited by gefitinib treatment only in the H3255 cell line. These findings further characterize a mechanism by which gefitinib treatment of NSCLC harboring EGFRL858R leads to a dramatic response to gefitinib.

Original languageEnglish (US)
Pages (from-to)7241-7244
Number of pages4
JournalCancer Research
Issue number20
StatePublished - Oct 15 2004
Externally publishedYes


Dive into the research topics of 'Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255'. Together they form a unique fingerprint.

Cite this