title: Role of lifeguard β-isoform in the development of breast cancer.
abstract: In the last century there has been great progress in the treatment of breast cancer by improving drug and radiation therapy as well as surgical techniques. Despite this development, breast cancer remains a major cause of death among women in Europe and the US. The cause of breast cancer at the cellular level is still not fully understood. In the present study, we investigated the expression of the Lifeguard β-isoform in breast cancer tissues. In contrast to Lifeguard, the β‑isoform has one transmembrane domain less, which is the last of seven (99 bp), and due to this we suspect that the Lifeguard β-isoform exhibits a different function. We determined the expression and function of the β-isoform of Lifeguard in breast cancer cell lines (MCF-7 and MDA-MB-231), a human breast epithelial cell line (MCF10A) and in breast tumour tissue sections. Western blotting, PCR arrays and immunofluorescence were used to investigate the expression of Lifeguard and its β-isoform. Moreover, we investigated the ability of Lifeguard β-isoform expression to inhibit apoptosis induced by Fas. Our results indicated that Lifeguard β-isoform is strongly expressed in breast tumour tissues. More notably, we demonstrated that Fas sensitivity was reduced in the MCF10A breast cells expressing the Lifeguard β-isoform. Taken together, our findings indicate the role of the Lifeguard β-isoform as an anti‑apoptotic protein and provide further evidence of the potential of the Lifeguard β-isoform as a target for the development of novel therapeutic strategies.
authors: Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, D-30659 Hannover, Germany.
authors: Nadjib
authors: N
authors: Dastagir
authors: Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, D-30659 Hannover, Germany.
authors: Andrea
authors: A
authors: Lazaridis
authors: Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, D-30659 Hannover, Germany.
authors: Khaled
authors: K
authors: Dastagir
authors: Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, D-30659 Hannover, Germany.
authors: Kerstin
authors: K
authors: Reimers
authors: Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, D-30659 Hannover, Germany.
authors: Peter M
authors: PM
authors: Vogt
authors: Department of Plastic, Hand and Reconstructive Surgery, Hannover Medical School, D-30659 Hannover, Germany.
authors: Vesna
authors: V
authors: Bucan
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D042361:Mammary Glands, Human / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C400427:FAIM2 protein, human; C491901:FAS protein, human; D008565:Membrane Proteins; D020033:Protein Isoforms; D019014:fas Receptor