Investigating the role of lysyl oxidase (LOX) in renal cell carcinoma development


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Abdul Karim Fallah (1), Qiuyu Wang (1), John Gaffney (1), Pat Kumar (1), Shant Kumar (1), Mark Slevin (1)
Manchester Metropolitan University, Manchester, United Kingdom (1)

Background

Kidney tumours represent 3% of all adult malignancies. Compared with other cancers, renal cell carcinomas (RCC) are relatively rare, but worldwide incidence and mortality rates are steadily rising at a rate of approximately 2-3%. Clear cell RCC (ccRCC) is the most common type of RCC, representing 70-75% of all types. The pathogenesis of ccRCC remains unclear. To understand the molecular mechanisms that underlie the development of ccRCC, the gene expression profile of ccRCC was analyzed. Lysyl oxidase (LOX), an extracellular enzyme gene, was found up-regulated in ccRCC.

Method

Paired ccRCC tumours and corresponding normal looking renal tissues were collected. RNAs were extracted using TRIzol. Variations in gene expressions between ccRCC and normal renal tissue were analysed using Affymetrix microarray. RT-PCR and western blotting were used to verify the microarray data.

Caki-2 cells were cultured in a modified McCoy’s 5a medium.  To determine the effects of LOX enzymatic activity in ccRCC, Caki-2 cells were treated with increasing concentrations of beta-aminopropionitrile (BAPN), and cell proliferation, migration, invasion and apoptosis were assessed in vitro.

Results

In total, 308 genes were up- or down-regulated over 1.5 fold in ccRCC compared with those in the normal renal samples. An up-regulation of LOX in ccRCC samples relative to their normal counterparts was identified and it was confirmed by RT-PCR and western blotting assays.

A significant inhibition on Caki-2 cell proliferation, migration and invasion was shown following the addition of BAPN to cells, and the inhibitory effects were related to LOX expression levels.

Conclusion

An altered expression of LOX in ccRCC tissues may serve as a molecular marker for the tumour diagnosis. These results also suggest that LOX may contribute to ccRCC development through influencing clear cell proliferation, migration and invasion, therefore might use as candidate therapeutic targets of ccRCC.

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