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.