Isolation and characterization of PAGE-1 and GAGE-7. New genes expressed in the LNCaP prostate cancer progression model that share homology with melanoma-associated antigens

J Biol Chem. 1998 Jul 10;273(28):17618-25. doi: 10.1074/jbc.273.28.17618.

Abstract

The LNCaP progression model of human prostate cancer consists of lineage-related sublines that differ in their androgen sensitivity and metastatic potential. A differential display polymerase chain reaction was employed to evaluate mRNA expression differences between the LNCaP sublines in order to define the differences in gene expression between the 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. Hybridization screening of a lambda gt11 expression library with BG16.21 revealed two transcripts, both homologous to BG16.21 at the 3' end. A GenBankTM data base search using the GCG Wisconsin software package revealed the shorter approximately 600-bp transcript (designated GAGE-7) to be a new member of the GAGE family. The second approximately 700-bp transcript was a novel gene (designated PAGE-1, "prostate associated gene") with only 45% homology to GAGE gene family members. RNA blot analysis demonstrated that GAGE-7 mRNA was expressed at equal levels in all lineage related prostate cancer cell sublines, while PAGE-1 mRNA levels were elevated 5-fold in C4-2 and C4-2B as compared with LNCaP cells. Neither 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 expression was found to be restricted to testes (high) and placenta (low) on human multiple tissue Northern blots. As GAGE/MAGE antigens were reported previously to be targets for tumor-specific cytotoxic lymphocytes in melanoma, these results suggest that PAGE-1 and GAGE-7 may be related to prostate cancer progression and may serve as potential targets for novel therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Neoplasm / genetics*
  • Base Sequence
  • DNA, Complementary
  • Humans
  • Male
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Sequence Homology, Amino Acid
  • Sequence Homology, Nucleic Acid
  • Tumor Cells, Cultured

Substances

  • Antigens, Neoplasm
  • DNA, Complementary
  • GAGE7 protein, human
  • Neoplasm Proteins
  • PAGE1 protein, human

Associated data

  • GENBANK/AF058988
  • GENBANK/AF058989