Researchers have said that about one-third of cases of Wilms tumor, a pediatric cancer of the kidney, are linked to a gene called Lin28.
Studies in the mouse model further suggest that controlled expression of Lin28 can promote kidney development and therefore may hold clues to regeneration of damaged kidneys in adults.
When examined under a microscope, the tumors resemble immature embryonic kidneys, leading doctors to conclude that Wilms tumors form when kidney development, normally complete by birth, persists into childhood.
Lin28 is closely tied to organ and tissue development in organisms as diverse as worms and humans, and is active in the kidneys early in development.
To see whether Lin28 might be a factor in Wilms tumor development, Daley and an international team of collaborators measured the gene's expression in tumor samples from 105 Wilms patients.
Achia Urbach, PhD, lead author on the study, engineered a strain of mice to express a Lin28 transgene in the kidneys. The kidneys of those mice were markedly enlarged and continued to grow as long as the Lin28 gene was active. Eventually, those kidneys took on the appearance of Wilms tumors.
Daley and Urbach's team found that they could reverse Lin28's tumor-causing effects in their transgenic model by forcing expression of Let-7, suggesting that treatments targeting Lin28 hold promise for treating Wilms tumors.
The team's insights into the origins of kidney cancer have implications for promoting kidney growth and regeneration.
The study has been published online in the journal Genes and Development.