S100A2 is strongly expressed in airway basal cells, preneoplastic bronchial lesions and primary non-small cell lung carcinomas.
S100A2 gene products were shown to be frequently and dramatically over-represented in non-small cell lung cancer (NSCLC) lesions over normal tissue by microarray analysis. We have now analysed an independent series of NSCLC tumours and multiple matched normal bronchial epithelial sites by RT-PCR and immunohistochemistry to investigate: whether this expression pattern can be confirmed and whether elevated expression is associated with tumour histology, clinical outcome or preneoplasia. In this second series, S100A2 was strongly expressed in 76% (35 out of 46) of tumours, more frequently in squamous cell than adenocarcinomas (P<0.002). This strong expression was not related to high-level gene amplification, but was associated in one of five informative cases with an allele-specific imbalance in transcript levels. Most tumours strongly expressed the DeltaNp63 transcript, the product of which is a putative regulator of S100A2 transcription and while all but one of the tumours positive for DeltaNp63 expressed S100A2, others negative for this regulator also expressed the gene. Contrary to the hypothesis that S100A2 is a tumour suppressor, no somatic mutations were identified in the coding sequence in 44 tumours. Furthermore, an examination of multiple tumour-free epithelial sites from 20 patients showed that strong expression was often associated with increasing levels of disorder in preinvasive bronchial lesions (P<0.0001).
Gene Function Group, Roy Castle Lung Cancer Programme (Clinical Dental Sciences), University of Liverpool Cancer Research Centre, 200 London Road, Liverpool L3 9TA, UK.
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SL
Smith
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M
Gugger
P
P
Hoban
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D
Ratschiller
S G
SG
Watson
J K
JK
Field
D C
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Betticher
J
J
Heighway
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022981:Allelic Imbalance; D014408:Biomarkers, Tumor / Q000378:metabolism; D001980:Bronchi / Q000378:metabolism / Q000473:pathology*; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002630:Chemotactic Factors / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D018295:Neoplasms, Basal Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D014408:Biomarkers, Tumor; D002630:Chemotactic Factors; D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D009418:S100 Proteins; C098997:S100A2 protein, human; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins