ISOLATION AND CHARACTERIZATION OF PAGE-1 AND GAUGE-7 - NEW GENES EXPRESSED IN THE LNCAP PROSTATE-CANCER PROGRESSION MODEL THAT SHARE HOMOLOGY WITH MELANOMA-ASSOCIATED ANTIGENS

The LNCaP progression model of human prostate cancer consists of linea ge-related sublines that differ in their androgen sensitivity and meta static potential. A differential display polymerase chain reaction was employed to evaluate mRNA expression differences between the LNCaP su blines in order to define the differences in gene expression between t he androgen-sensitive, nontumorigenic LNCaP cell line and the androgen -insensitive, metastatic LNCaP sublines, C4-2 and C4-2B. An amplicon, BG16.21, was isolated that showed increased expression in the androgen -independent and metastatic LNCaP sublines, C4-2 and C4-2B. Hybridizat ion screening of a lambda gt11 expression library with BG16.21 reveale d two transcripts, both homologous to BG16.21 at the 3' end, A GenBank (TM) data base search using the GCG Wisconsin software package reveale d the shorter similar to 600-bp transcript (designated GAGE-7) to be a new member of the GAGE family, The second similar to 700-bp transcrip t was a novel gene (designated PAGE-1, ''prostate associated gene'') w ith only 45% homology to GAGE gene family members. RNA blot analysis d emonstrated that GAGE-7 mRNA was expressed at equal levels in all line age related prostate cancer cell sublines, while PAGE-1 mRNA levels we re elevated 5-fold in C4-2 and C4-2B as compared with LNCaP cells, Nei ther GAGE-7 nor PAGE-1 demonstrated any regulation by androgens in the prostate cancer cell lines used in this study. PAGE-1 and GAGE-7 expr ession was found to be restricted to testes (high) and placenta (low) on human multiple tissue Northern blots. As GAGE/MAGE antigens were re ported preciously to be targets for tumor-specific cytotoxic lymphocyt es in melanoma, these results suggest that PAGE-1 and GAGE-7 may be re lated to prostate cancer progression and may serve as potential target s for novel therapies.