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Pronapsin A and B gene expression in normal and malignant human lung and mononuclear blood cells.

Abstract
The two human pronapsin genes which are located immediately adjacent to one another on chromosome 19 were shown, using quantitative RT-PCR, to have distinctly different expression patterns. Transcription of the pronapsin A gene in normal human lung tissue was not appreciably altered in lung carcinomas and comparable pronapsin A mRNA levels were also quantified in lung epithelial cell lines and in tumour cell lines originating from human lung epithelium. Pronapsin A may thus have considerable diagnostic value as a marker for primary lung cancer. In contrast, the pronapsin B gene, which lacks an in-frame stop codon and so may be a transcribed pseudogene, is expressed at comparable levels in normal human spleen, thymus, cytotoxic and helper T-lymphocytes, natural killer (NK) cells and B-lymphocytes. The mRNA levels quantified in B-cells from adults with chronic lymphoblastic leukaemia were not significantly different from those measured in B-cells from healthy individuals. Similarly, comparable levels of expression were quantified in monocytes from healthy individuals and from a patient with acute myeloid leukaemia, whereas in alveolar macrophages, which are terminally differentiated myeloid cells, transcription of the pronapsin B gene was down-regulated by approximately one order of magnitude. Reciprocally, an approximately 20-fold up-regulation in expression of the procathepsin D gene in the macrophages relative to the circulating monocytes was revealed by quantitative measurements made in parallel throughout all of this study for the respective mRNAs encoding the intracellular aspartic proteinases, procathepsin D and procathepsin E. Thus, while there appears to be little difference in expression of the pronapsin A and B genes between healthy and malignant human cells and tissues, the reciprocal alterations in the levels of transcription of the pronapsin B and procathepsin D genes may have significance in the developmental processes associated with myeloid cell differentiation into macrophages.
AuthorsMatthew Cook, Frank Bühling, Siegfried Ansorge, Peter J Tatnell, John Kay
JournalBiochimica et biophysica acta (Biochim Biophys Acta) Vol. 1577 Issue 1 Pg. 10-6 (Aug 19 2002) ISSN: 0006-3002 [Print] Netherlands
PMID12151090 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Enzyme Precursors
  • Protein Isoforms
  • RNA, Messenger
  • Aspartic Acid Endopeptidases
  • pronapsin
  • Cathepsin E
  • Cathepsin D
Topics
  • Acute Disease
  • Aspartic Acid Endopeptidases (biosynthesis, genetics)
  • Carcinoma (enzymology, genetics)
  • Cathepsin D (biosynthesis, genetics)
  • Cathepsin E (biosynthesis, genetics)
  • Cells, Cultured
  • Enzyme Precursors (biosynthesis, genetics)
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell (enzymology, genetics)
  • Leukemia, Myeloid (enzymology, genetics)
  • Leukocytes, Mononuclear (enzymology)
  • Lung (enzymology)
  • Lung Neoplasms (enzymology, genetics)
  • Lymphocytes (enzymology)
  • Myeloid Cells (enzymology)
  • Protein Isoforms (biosynthesis, genetics)
  • RNA, Messenger (biosynthesis)
  • Spleen (enzymology)
  • Thymus Gland (enzymology)
  • Transcription, Genetic

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