CLAR1, a novel gene that exhibits enhanced expression in advanced human prostate cancer

The molecular events involved in prostate cancer progression are, at presen t, poorly understood. Using a differential display technique, we identified a cDNA fragment that is present in greater abundance in stage D prostate t umors compared to stage B tumors. Northern analysis was used to confirm tha t transcripts for this gene are expressed at higher levels in prostate tumo rs of later pathological stage and higher Gleason grade compared to tumors of earlier stage and lower grade. These transcripts were also expressed at high levels in all four human prostate cancer cell lines, the neonatal pros tate cell line FNC 267 beta 1, and in a variety of other normal human adult and fetal tissues. The cDNA fragment obtained by differential display was used as a probe to clone the full-length cDNA for this gene from a human he art cDNA library, DNA sequence analysis confirmed that the cDNA was novel, and we have named this gene CLAR1, The gene displays two transcripts of 2.6 and 2.0 kb in all tissues examined. CLAR1 maps to chromosome 19q13.3 and a ppears highly conserved among mammals. The deduced amino acid sequence of C LAR1 encodes a proline-rich protein that contains several SH3-binding domai ns and a serine phosphorylation site. The presence of these motifs suggests a possible role for CLAR1 in one or more signal transduction pathways. The enhanced expression of this novel gene in more advanced forms of prostate cancer and its potential role in signal transduction both argue that this g ene should be further investigated.