Journal article

Mammary-specific ablation of Cyp24a1 inhibits development, reduces proliferation and increases sensitivity to vitamin D

Lei Sheng, Andrew G Turner, Kate Barratt, Richard Kremer, Howard A Morris, David F Callen, Paul H Anderson, Gerard A Tarulli

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2019

Abstract

Active vitamin D (1,25(OH)2D) has been shown to regulate numerous cell processes in mammary cells. Degradation of 1,25(OH)2D is initiated by the mitochondrial enzyme, 25-hydroxyvitamin D 24-hydroxylase (CYP24 A1), and provides local control of 1,25(OH)2D bioactivity. Several reports of the association between elevated CYP24 A1 activity and breast cancer incidence, suggest that CYP24 A1 may be a target for therapeutic intervention. Whether CYP24 A1 activity within the mammary epithelium regulates 1,25(OH)2D levels and mammary gland development is yet to shown. We have used a conditional knockout of the Cyp24a1 gene specifically in the mammary epithelium to demonstrate reduced terminal end bud..

View full abstract

University of Melbourne Researchers

Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Canadian Institute for Health Research


Awarded by National Breast Cancer Foundation


Funding Acknowledgements

This study was supported by the National Health and Medical Research Council of Australia (Grant: AP1009438), the Canadian Institute for Health Research (MOP 10839 - RK), and the National Breast Cancer Foundation (PS-15-041-GT). LS was sponsored by the China Scholarship Council (CSC).