MLN64 EXHIBITS HOMOLOGY WITH THE STEROIDOGENIC ACUTE REGULATORY PROTEIN (STAR) AND IS OVER-EXPRESSED IN HUMAN BREAST CARCINOMAS

The MLN64 gene, which is localized in q12-q21 of the human chromosome 17, encodes a novel protein containing 2 distinct domains. At the N-te rminal, MLN64 exhibits a potential trans-membrane region, while at the C-terminal, it shares homology with the F26F4.4 protein of Caenorhabd itis elegans and the steroidogenic acute regulatory (StAR) protein, a mitochondrial protein which is involved in steroid-hormone synthesis. By comparing the C-terminal part of these proteins, we defined a novel protein domain, which we termed SHD for ''StAR Homology Domain'', Of the 93 primary invasive breast carcinomas that were examined, 14 were found to over-express MLN64. These 14 tumors also expressed high c-erb B-2 transcript levels, which were not detected in the MLN64-negative t umors. MLN64 mRNA and protein were specifically detected in malignant cells of breast carcinomas. MLN64 protein was localized within bundle- like structures distributed throughout the cell cytoplasm and condense d in a perinuclear patch, suggesting an association with a specific ce ll compartment. When the N-terminal part of MLN64 was deleted, MLN64 w as uniformly distributed in the cell cytoplasm, indicating that N-term inal part is involved in the specific cytoplasmic localization of MLN6 4. The homology between the C-terminal part of MLN64 and the functiona l StAR domain (SHD) suggests that MLN64 and StAR, although distributed in different cellular compartments, may both play a role in steroidog enesis, In this case, the high levels of MLN64 observed in some breast carcinomas could contribute to the progression of these tumors throug h increased intratumoral steroidogenesis. (C) 1997 Wiley-Liss, Inc.