title: AZU-1: a candidate breast tumor suppressor and biomarker for tumor progression.
abstract: To identify genes misregulated in the final stages of breast carcinogenesis, we performed differential display to compare the gene expression patterns of the human tumorigenic mammary epithelial cells, HMT-3522-T4-2, with those of their immediate premalignant progenitors, HMT-3522-S2. We identified a novel gene, called anti-zuai-1 (AZU-1), that was abundantly expressed in non- and premalignant cells and tissues but was appreciably reduced in breast tumor cell types and in primary tumors. The AZU-1 gene encodes an acidic 571-amino-acid protein containing at least two structurally distinct domains with potential protein-binding functions: an N-terminal serine and proline-rich domain with a predicted immunoglobulin-like fold and a C-terminal coiled-coil domain. In HMT-3522 cells, the bulk of AZU-1 protein resided in a detergent-extractable cytoplasmic pool and was present at much lower levels in tumorigenic T4-2 cells than in their nonmalignant counterparts. Reversion of the tumorigenic phenotype of T4-2 cells, by means described previously, was accompanied by the up-regulation of AZU-1. In addition, reexpression of AZU-1 in T4-2 cells, using viral vectors, was sufficient to reduce their malignant phenotype substantially, both in culture and in vivo. These results indicate that AZU-1 is a candidate breast tumor suppressor that may exert its effects by promoting correct tissue morphogenesis.
authors.affiliation: Lawrence Berkeley National Laboratory, Life Sciences Division, Berkeley, California 94720, USA.
authors.forename: H M
authors.initials: HM
authors.lastname: Chen
authors.forename: K L
authors.initials: KL
authors.lastname: Schmeichel
authors.forename: I S
authors.initials: IS
authors.lastname: Mian
authors.forename: S
authors.initials: S
authors.lastname: Lelièvre
authors.forename: O W
authors.initials: OW
authors.lastname: Petersen
authors.forename: M J
authors.initials: MJ
authors.lastname: Bissell
mesh_terms: D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms; D002352:Carrier Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D011230:Precancerous Conditions; D017434:Protein Structure, Tertiary; D012334:RNA, Neoplasm / Q000032:analysis; D016415:Sequence Alignment; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D012334:RNA, Neoplasm; C410333:TACC2 protein, human; D025521:Tumor Suppressor Proteins