Rab24 protein levels show dynamic changes in mouse tissues and human cancers

Abstract

<p>Rab24 is an unusual member of the Rab family of small GTPases, implicated in autophagy, endocytosis and cell division. In order to elucidate possible organ and age-specific roles of Rab24, we investigated tissue-specific levels of Rab24 in mice by western blotting and immunohistochemistry from postnatal day one to 9 months of age. In adult mice, the highest protein levels were found in the brain followed by the kidney, whereas lower levels were detected in the pancreas, spleen, liver, lung, heart, and skeletal muscle. Dynamic changes in Rab24 levels were observed during early postnatal development, with a sharp increase in the brain at postnatal day 14, after which the level remained high into adulthood. In the heart, skeletal muscle, pancreas and liver, higher Rab24 levels were observed during the first two postnatal weeks, after which the levels dropped and stayed low until adulthood. The age-dependent changes suggest age- and organ-specific regulation of Rab24 protein levels and possible organ-specific roles for Rab24 in development and maturation. Immunohistochemistry of the brain revealed that Rab24 was mostly present in neuronal cells in 1-month-old and older mice. Also, epithelial cells in several tissues showed high Rab24 levels. These results suggest possible roles for Rab24 in neuronal and epithelial maintenance. We further analysed immunohistochemical staining for RAB24 in human cancers and normal tissues. RAB24 staining in cancers of the breast and skin was higher than in the corresponding normal tissues, while it was reduced in cancers of the digestive system and the urinary tract. We also observed elevated RAB24 staining in medulloblastoma and neuroblastoma, two paediatric cancers of neuronal origin. In pancreatic neuroendocrine tumours that originate from islet cells, RAB24 levels were lower than in normal pancreatic islet cells. Collectively, our findings provide a comprehensive overview of RAB24 protein levels across mouse tissues and a wide spectrum of human cancers. The observed differences in RAB24 levels between cancer types and between malignant and normal tissues, suggest that RAB24 may serve as a potential diagnostic or differentiation marker in specific tumour types.<br></p>