title: Expressions of topoisomerase IIα and BCRP in metastatic cells are associated with overall survival in small cell lung cancer patients.
abstract: The aim of this study was to investigate the mRNA expression levels of multidrug resistance-associated proteins in chemo-naïve metastatic lung cancer cells and to determine the correlation with response to chemotherapy and overall survival. Metastatic cells were obtained by transbronchial fine needle aspiration biopsy of enlarged mediastinal lymph nodes in 14 patients with small cell lung cancer (SCLC) and 7 patients with non-small cell lung cancer (NSCLC). After cytological confirmation of lung cancer type, total RNA was extracted from biopsy samples and reverse transcribed to cDNA, and real-time PCR for the genes of interest [P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance protein (LRP) and topoisomerase IIα (TOPIIα)], was performed. We observed significantly decreased expression of BCRP and significantly increased expression of TOPIIα in metastatic SCLC cells compared to NSCLC. Furthermore, in SCLC high topoisomerase IIα and low BCRP expression levels positively correlated with longer overall survival. Our results showed higher expression levels of BCRP as well as lower levels of topoisomerase IIα in chemo-naïve metastatic cells in NSCLC than in SCLC. These results correlate with previous observations that metastatic SCLC cells at the beginning of chemotherapy are potentially more sensitive to chemotherapeutic agents while in metastatic NSCLC cells resistance is usually inherent. We also showed that altered levels of topoisomerase IIα and BCRP in SCLC are important factors that contribute to resistance to chemotherapeutics that interfere with the enzyme and/or DNA and are highly associated with overall survival.
authors: University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia. matija.rijavec@klinika-golnik.si
authors: Matija
authors: M
authors: Rijavec
authors: Mira
authors: M
authors: Silar
authors: Nadja
authors: N
authors: Triller
authors: Izidor
authors: I
authors: Kern
authors: Urška
authors: U
authors: Cegovnik
authors: Mitja
authors: M
authors: Košnik
authors: Peter
authors: P
authors: Korošec
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D015251:Epirubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000556:secondary; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics; D014750:Vincristine / Q000008:administration & dosage; D000099187:Major Vault Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D002945:Cisplatin; D003520:Cyclophosphamide; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D015251:Epirubicin; D005047:Etoposide; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D020394:Vault Ribonucleoprotein Particles; D014750:Vincristine; D000099187:Major Vault Protein; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1