LOSS OF SPR1 EXPRESSION MEASURABLE BY QUANTITATIVE RT-PCR IN HUMAN BRONCHOGENIC-CARCINOMA CELL-LINES

Expression of the small, proline-rich protein (spr1) squamous differen tiation marker was measured in five cultured normal and 12 malignant h uman bronchial epithelial cell (BEC) populations by quantitative rever se transcriptase polymerase chain reaction (RT-PCR). Whereas spr1 expr ession was quantifiable and inducible in all five cultured normal cell populations, in all 12 carcinoma cell lines evaluated it was neither quantifiable nor inducible. Primers spanning the entire spr1 coding se quence amplified full-length PCR product from genomic DNA; therefore, large deletions in the coding region were not responsible for the loss of expression measurable by RT-PCR. This is the first molecular genet ic marker reported that distinguishes all normal from all carcinoma ce ll populations evaluated. Because the spr1 protein is a component of t he crosslinked envelope that forms during the squamous differentiation process, we hypothesize that the apparent loss of spr1 gene expressio n disrupts mechanisms for terminal squamous differentiation in the bro nchial epithelium, thereby contributing to malignant transformation.