S100A2 is strongly expressed in airway basal cells, preneoplastic bronchial lesions and primary non-small cell lung carcinomas

S L Smith; M Gugger; P Hoban; D Ratschiller; S G Watson; J K Field; D C Betticher; J Heighway

doi:10.1038/sj.bjc.6602188

S100A2 is strongly expressed in airway basal cells, preneoplastic bronchial lesions and primary non-small cell lung carcinomas

Br J Cancer. 2004 Oct 18;91(8):1515-24. doi: 10.1038/sj.bjc.6602188.

Authors

S L Smith¹, M Gugger, P Hoban, D Ratschiller, S G Watson, J K Field, D C Betticher, J Heighway

Affiliation

¹ Gene Function Group, Roy Castle Lung Cancer Programme (Clinical Dental Sciences), University of Liverpool Cancer Research Centre, 200 London Road, Liverpool L3 9TA, UK.

Abstract

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).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / genetics
Adenocarcinoma / metabolism
Adenocarcinoma / pathology
Adult
Aged
Aged, 80 and over
Allelic Imbalance
Biomarkers, Tumor / metabolism
Bronchi / metabolism
Bronchi / pathology*
Carcinoma, Large Cell / genetics
Carcinoma, Large Cell / metabolism*
Carcinoma, Large Cell / pathology
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / metabolism*
Carcinoma, Non-Small-Cell Lung / pathology
Carcinoma, Squamous Cell / genetics
Carcinoma, Squamous Cell / metabolism
Carcinoma, Squamous Cell / pathology
Chemotactic Factors / genetics
Chemotactic Factors / metabolism*
DNA-Binding Proteins
Epithelial Cells / metabolism
Epithelial Cells / pathology
Female
Gene Amplification
Gene Expression Regulation, Neoplastic*
Genes, Tumor Suppressor
Humans
Lung Neoplasms / genetics
Lung Neoplasms / metabolism*
Lung Neoplasms / pathology
Male
Middle Aged
Neoplasms, Basal Cell / genetics
Neoplasms, Basal Cell / metabolism
Neoplasms, Basal Cell / pathology
Phosphoproteins / metabolism
Precancerous Conditions / metabolism*
Precancerous Conditions / pathology
S100 Proteins / genetics
S100 Proteins / metabolism*
Trans-Activators / metabolism
Transcription Factors
Tumor Suppressor Proteins

Substances

Biomarkers, Tumor
Chemotactic Factors
DNA-Binding Proteins
Phosphoproteins
S100 Proteins
S100A2 protein, human
TP63 protein, human
Trans-Activators
Transcription Factors
Tumor Suppressor Proteins