PINK1 displays tissue-specific subcellular location and regulates apoptosis and cell growth in breast cancer cells.
The PINK1 gene is mutated in the germ line of patients with hereditary early-onset Parkinson disease, and PINK1 prosurvival function at neuronal mitochondria has been related with the etiology of this disease. However, the expression and function of PINK1 protein in nonneuronal tissues has not been determined yet. Here, we have analyzed PINK1 protein expression and subcellular distribution in normal and neoplastic human tissues and investigated the function of PINK1 in breast carcinoma cells. PINK1 protein, as stained by a specific anti-PINK1 monoclonal antibody, was widely expressed in human tissues, displaying high expression in epithelial tissues and in the central nervous system and lower expression in tissues of mesenchymal origin. The subcellular distribution of PINK1 was cytoplasmic granular or cytoplasmic diffuse in most tissues. In breast, PINK1 was also associated with the plasma membrane. Human neoplastic tissues ranged from high PINK1 expression in carcinomas to low expression in sarcomas. In neoplastic tissues, PINK1 displayed a diffuse cytoplasmic localization, with an additional membranous localization in breast carcinoma and squamous carcinoma of lung. In the human breast carcinoma Michigan Cancer Foundation-7 cell line, ectopic expression of cytoplasmic or mitochondrial-targeted PINK1 inhibited apoptosis triggered by hydrogen peroxide and suppressed cell growth in soft agar, whereas PINK1 silencing increased hydrogen peroxide-induced apoptosis. Together, our findings indicate that the physiologic functions of PINK1 go beyond its regulatory role of mitochondria-mediated cell survival in neurons.
Laboratorio de Biología Molecular del Cáncer, Centro de Investigación Príncipe Felipe, 46013 Valencia, Spain.
Arnaud
A
Berthier
Samuel
S
Navarro
Judit
J
Jiménez-Sáinz
Isabel
I
Roglá
Francisca
F
Ripoll
Javier
J
Cervera
Rafael
R
Pulido
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D008297:Male; D051379:Mice; D011494:Protein Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D014018:Tissue Distribution; D000099202:PTEN-Induced Putative Kinase
D011494:Protein Kinases; D000099202:PTEN-Induced Putative Kinase