AZU-1: a candidate breast tumor suppressor and biomarker for tumor progression.
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.
Chen
H M
HM
Lawrence Berkeley National Laboratory, Life Sciences Division, Berkeley, California 94720, USA.
Schmeichel
K L
KL
Mian
I S
IS
Lelièvre
S
S
Petersen
O W
OW
Bissell
M J
MJ
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
D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D012334:RNA, Neoplasm; C410333:TACC2 protein, human; D025521:Tumor Suppressor Proteins