CLAR1, a Novel Gene That Exhibits Enhanced Expression in Advanced Human Prostate Cancer

• Published in: Clinical cancer research Vol. 5; no. 6; pp. 1595 - 1602
• Main Authors: RONDINELLI, R. H, TRICOLI, J. V
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.06.1999
• Subjects: Adaptor Proteins, Signal Transducing; Alternative Splicing; Amino Acid Sequence; Biological and medical sciences; Blotting, Northern; Chromosome Mapping; Chromosomes, Human, Pair 19 - genetics; Cloning, Molecular; Gene Expression; Humans; In Situ Hybridization, Fluorescence; Male; Medical sciences; Molecular Sequence Data; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Nephrology. Urinary tract diseases; Organ Specificity - genetics; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured; Tumors of the urinary system; Urinary tract. Prostate gland; Genetic mapping; Human; Urinary system disease; Prostate disease; Gene product; Tumoral tissue; Malignant tumor; Gene expression; In vitro; Chromosome F19; Established cell line; Genetics; Advanced stage; Male genital diseases; Prostate; Tumor cell
• ISSN: 1078-0432; 1557-3265

The molecular events involved in prostate cancer progression are, at present, poorly understood. Using a differential display technique, we identified a cDNA fragment that is present in greater abundance in stage D prostate tumors compared to stage B tumors. Northern analysis was used to confirm that transcripts for this gene are expressed at higher levels in prostate tumors 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 prostate cell line FNC 267β1, 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 heart 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 appears highly conserved among mammals. The deduced amino acid sequence of CLAR1 encodes a proline-rich protein that contains several SH3-binding domains 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 gene should be further investigated.