A role for a tumour suppressor in prostate gland architecture

Disorganised region of a prostate gland
Disorganised region of a prostate gland from a Dkk-3 mutant mouse showing E-cadherin in green, ZO1 in red and nuclei in blue

Researchers from the Department of Surgery and Cancer have uncovered a novel link between the tumour suppressor Dickkopf-3 (Dkk-3) and TGF-β signalling. The team previously found that Dkk-3 is required for human prostate epithelial cells to form acinar structures in 3D matrigel cultures; an in vitro model for prostate gland development.

This new study, carried out in collaboration with the Centre for Cooperative Research in Biosciences (CIC bioGUNE) in Bilbao and the German Cancer Research Center (DKFZ) in Heidelberg, shows that Dkk-3 limits epithelial cell proliferation in 3D cultures and during mouse prostate gland development. It is well known that TGF-β signals go awry during cancer progression; switching from tumour suppression to tumour promotion. This study shows that loss of Dkk-3 activates TGF-β signalling – inhibition of which rescues the 3D phenotype.

The results provide further support and rationale for the use of TGF-β inhibitors to treat prostate cancer. They may also be relevant to other cancers, such as those of the breast and the ovary, where similar changes in Dkk-3 and the TGF-β response take place. The studies at Imperial were carried out by Diana Romero and Yoshiaki Kawano, now at Kumamoto University in Japan, and were funded by a Cancer Research UK (CRUK) Project Grant awarded to Robert Kypta and Jonathan Waxman.

The work is published in the Journal of Cell Science.

Dr Robert M Kypta
Lecturer in Prostate Cancer
Department of Surgery & Cancer

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