Cloning and characterization of ectopically expressed transcripts for the actin-binding protein MIPP in mouse mammary carcinomas.

ABSTRACT

Mipp is a kelch-related, placental-specific gene that is ectopically expressed in many BALB/c mouse mammary carcinomas of various etiologies. The Kelch family encompasses proteins that are emerging as key links between microfilaments and a variety of cellular structures and functions. Mouse mammary tumors express two mipp transcripts (2.2 and 5.6 kb). We cloned the 2.2 kb mipp mRNA and analysed the product of its 1.7 kb ORF. The 584 residue MIPP protein has an N-terminal BTB domain and six C-terminal tandem Kelch repeats. Despite expression of two mipp RNAs, only a single MIPP protein is expressed in mammary tumors. MIPP protein binds to microfilaments in vitro and co-immunoprecipitates with actin. MIPP co-localized with concanavalin A at the endoplasmic reticulum, suggesting that MIPP might mediate interactions between microtubules and actin filaments. Because MIPP expression is widespread in mouse mammary tumors, it might contribute to tumorigenesis. Although MIPP had little effect on the growth rate of human breast cell lines following transfection, it greatly reduced the formation of duct-like structures on reconstituted basement membrane. Our results suggest that MIPP could contribute to malignant progression in the mouse mammary epithelial cells by perverting their response to cues from the extracellular matrix.