SPR1: An Early Molecular Marker for Bronchial Carcinogenesis

Tumorigenesis of the bronchial epithelium occurs through multiple and sequential morphological and molecular changes (1 ). In the respiratory tract, the earliest detectable morphological change is squamous metaplasia of the tracheo-bronchial epithelium upon exposure to carcinogen (2 ) or chronic tobacco smoke (3 ,4 ). A small proline-rich protein, SPR1, is a component of cross-linked envelopes of squamous epithelial cells of the airway (5 ). We have demonstrated that SPR1 is overexpressed in association with squamous differentiation in the primary culture of monkey and human bronchial epithelial cells (6 ,7 ). However, its expression is markedly diminished or lost in lung carcinoma (8 ,9 ). Furthermore, we have shown that expression and regulation of SPR1 is closely linked to multistep carcinogenesis of lung cancer in a series of human bronchial epithelial cell lines representing different stages of malignant transformation (10 ). Early in the transformation of bronchial epithelial cells, SPR1 expression can be upregulated by a tumor promoter, phorbol ester, and down-regulated by a retinoid (6 ,7 ,10 ). Therefore, SPR1 appears to be a molecular marker for early transformation of the bronchial epithelium, and it may serve as an intermediate marker in chemoprevention of lung cancer.