title: Frequent down-regulation of pim-1 mRNA expression in non-small cell lung cancer is associated with lymph node metastases.
abstract: Pim kinases are emerging as important mediators of cytokine signalling pathways in hematopoietic cells, and contribute to the progression of certain leukemias and solid tumors. The mRNA expression of pim-1, a putative oncogenic serine-threonine kinase, was determined in non-small cell lung cancer (NSCLC) patients. Sixty-eight patients with potentially curative resections (R0 resections) for NSCLC in histopathological stages I-IIIA were included. An analysis of pim-1 mRNA expression was performed on paired tumor and normal lung tissue samples by quantitative real-time reverse transcriptase-PCR (RT-PCR) standardized for beta-actin. Pim-1 expression in the tumor (median 0.28) was significantly down-regulated (p<0.0001) compared to the paired normal tissue (median 4.96). Immunohistochemistry showed a strong expression of Pim-1 protein in the normal respiratory epithelium and a lower expression in the tumor cells. A significant association between the pim-1 down-regulation and occurrence of lymph node metastases (p=0.05) was detected. The down-regulation of pim-1 mRNA was demonstrated for 59 out of 68 lung cancer patients (86.8%). Down-regulation occurs already in the early stage of NSCLC and is either directly involved in the lymphatic progression in NSCLC or represents a surrogate marker.
authors.affiliation: Department of Visceral and Vascular Surgery, Laboratory for Molecular Oncology, University of Cologne, Kerpener Strasse 62, Cologne, Germany. ute.warnecke-eberz@uk-koeln.de
authors.forename: Ute
authors.initials: U
authors.lastname: Warnecke-Eberz
authors.forename: Elfriede
authors.initials: E
authors.lastname: Bollschweiler
authors.forename: Uta
authors.initials: U
authors.lastname: Drebber
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pohl
authors.forename: Stephan E
authors.initials: SE
authors.lastname: Baldus
authors.forename: Arnulf H
authors.initials: AH
authors.lastname: Hoelscher
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzger
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000556:secondary; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D012333:RNA, Messenger; C496634:PIM1 protein, human; D051573:Proto-Oncogene Proteins c-pim-1