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Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255.
Cancer Res 2004; 64(20):7241-4CR

Abstract

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 (EGFR(WT)) are sensitive to gefitinib with IC(50) values of 40 nmol/L and 2 micromol/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 micromol/L) leads to significant apoptosis accompanied by increased poly(ADP-ribose) polymerase cleavage only in the H3255 cell line, leads to G(1)-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 EGFR(L858R) leads to a dramatic response to gefitinib.

Authors+Show Affiliations

Lowe Center for Thoracic Oncology and Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15492241

Citation

Tracy, Sean, et al. "Gefitinib Induces Apoptosis in the EGFRL858R Non-small-cell Lung Cancer Cell Line H3255." Cancer Research, vol. 64, no. 20, 2004, pp. 7241-4.
Tracy S, Mukohara T, Hansen M, et al. Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. Cancer Res. 2004;64(20):7241-4.
Tracy, S., Mukohara, T., Hansen, M., Meyerson, M., Johnson, B. E., & Jänne, P. A. (2004). Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. Cancer Research, 64(20), pp. 7241-4.
Tracy S, et al. Gefitinib Induces Apoptosis in the EGFRL858R Non-small-cell Lung Cancer Cell Line H3255. Cancer Res. 2004 Oct 15;64(20):7241-4. PubMed PMID: 15492241.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255. AU - Tracy,Sean, AU - Mukohara,Toru, AU - Hansen,Mark, AU - Meyerson,Matthew, AU - Johnson,Bruce E, AU - Jänne,Pasi A, PY - 2004/10/20/pubmed PY - 2004/12/16/medline PY - 2004/10/20/entrez SP - 7241 EP - 4 JF - Cancer research JO - Cancer Res. VL - 64 IS - 20 N2 - 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 (EGFR(WT)) are sensitive to gefitinib with IC(50) values of 40 nmol/L and 2 micromol/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 micromol/L) leads to significant apoptosis accompanied by increased poly(ADP-ribose) polymerase cleavage only in the H3255 cell line, leads to G(1)-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 EGFR(L858R) leads to a dramatic response to gefitinib. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/15492241/Gefitinib_induces_apoptosis_in_the_EGFRL858R_non_small_cell_lung_cancer_cell_line_H3255_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=15492241 DB - PRIME DP - Unbound Medicine ER -