The role of PDLIM4/RIL gene in the development of breast cancer
PDLIM4 (PDZ and LIM domain protein 4) is an adaptor protein, encoded by the PDLIM4 gene. Epigenetic suppression of PDLIM4 is frequently associated with different types of cancer, particularly with breast cancer. The role of PDLIM4 in breast cancer development has not been sufficiently studied, so today there is no any theory, which could clearly explain correlation between changes in PDLIM4 expression and tumor progression. Previously, basing on our results, we had hypothesized a mechanism of Scribble-mediated participation of PDLIM4 in the development of breast cancer. According this theory RIL possibly interacts with Scribble - a membrane protein, which is involved in migration, proliferation and polarity of epithelial cells. The aim of the present research was to examine the subcellular colocalization of Scribble with different isoforms of PDLIM4, to verify the previously described hypothesis and reveal differences between alternative transcripts of PDLIM4.
At the first stage of our work we analyzed the expression of PDLIM4 in cells of different breast cancer cell lines. Among them we chose the cell cultures, which were characterized by expression of alternative transcripts of PDLIM4. The selected cells were used to examine differences in intracellular localization of alternative transcripts of PDLIM4 and compirison of this data with location of Scribble. The obtained data let us to estimate the relationships between Scribble and PDLIM4 and propose participation of single PDLIM4 isophorms in the process of Scribble-mediated epithelial-mesenchimal transition. Another outcome of our study was the finding, that alternative transcripts of PDLIM4 could be observed not only in cytoplasm, but into nucleus as well. The revealing of subnuclear localization of PDLIM4 let us to have another look on this protein, which had been previously described only as a cytoplasmic component.