MLN64 exhibits homology with the steroidogenic acute regulatory protein (STAR) and is over-expressed in human breast carcinomas.

Abstract:

: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-terminal, MLN64 exhibits a potential trans-membrane region, while at the C-terminal, it shares homology with the F26F4.4 protein of Coenorhabditis 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-erbB-2 transcript levels, which were not detected in the MLN64-negative tumors. 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 condensed in a perinuclear patch, suggesting an association with a specific cell compartment. When the N-terminal part of MLN64 was deleted, MLN64 was uniformly distributed in the cell cytoplasm, indicating that N-terminal part is involved in the specific cytoplasmic localization of MLN64. The homology between the C-terminal part of MLN64 and the functional StAR domain (SHD) suggests that MLN64 and StAR, although distributed in different cellular compartments, may both play a role in steroidogenesis. In this case, the high levels of MLN64 observed in some breast carcinomas could contribute to the progression of these tumors through increased intratumoral steroidogenesis.

journal_name

Int J Cancer

authors

Moog-Lutz C,Tomasetto C,Régnier CH,Wendling C,Lutz Y,Muller D,Chenard MP,Basset P,Rio MC

doi

10.1002/(sici)1097-0215(19970410)71:2<183::aid-ijc

subject

Has Abstract

pub_date

1997-04-10 00:00:00

pages

183-91

issue

2

eissn

0020-7136

issn

1097-0215

pii

10.1002/(SICI)1097-0215(19970410)71:2<183::AID-IJC

journal_volume

71

pub_type

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