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hAG-2 and hAG-3 are recently discovered human homologues of the secreted Xenopus laevis proteins XAG-1/2 (AGR-1/2) that are expressed in the cement gland, an ectodermal organ in the head associated with anteroposterior fate determination during early development. Although the roles of hAG-2 and hAG-3 in mammalian cells are unknown, both proteins share a high degree of protein sequence homology and lie adjacent to one another on chromosome 7p21. hAG-2 mRNA expression has previously been demonstrated in oestrogen receptor (ER)-positive cell lines. In this study, we have used real-time quantitative RT - PCR analysis and immunohistochemistry on tissue microarrays to demonstrate concordant expression of hAG-2 and hAG-3 mRNA and protein in breast tumour tissues. Tumour expression of both genes correlated with OR (hAG2, P=0.0002; hAG-3, P=0.0012), and inversely correlated with epidermal growth factor receptor (EGFR) (P=0.003). Yeast two-hybrid cloning identified metastasis-associated GPI-anchored C4.4a protein and extracellular alpha-dystroglycan (DAG-1) as binding partners for both hAG-2 and hAG-3, which if replicated in clinical oncology would demonstrate a potential role in tumour metastasis through the regulation of receptor adhesion and functioning. hAG-2 and hAG-3 may therefore serve as useful molecular markers and/or potential therapeutic targets for hormone-responsive breast tumours.

Original publication

DOI

10.1038/sj.bjc.6600740

Type

Journal article

Journal

Br J Cancer

Publication Date

24/02/2003

Volume

88

Pages

579 - 585

Keywords

Amino Acid Sequence, Antimicrobial Cationic Peptides, Breast Neoplasms, Carrier Proteins, Cell Adhesion Molecules, Cell Differentiation, Chromosomes, Human, Pair 7, Cytoskeletal Proteins, Dystroglycans, GPI-Linked Proteins, Gene Expression Regulation, Neoplastic, Humans, Magainins, Membrane Glycoproteins, Molecular Sequence Data, Neoplasm Metastasis, Neoplasm Proteins, Physical Chromosome Mapping, Plant Proteins, Protein Binding, RNA, Messenger, Receptors, Estrogen, Reverse Transcriptase Polymerase Chain Reaction, Two-Hybrid System Techniques, Xenopus Proteins