title: A comparison of vitamin D activity in paired non-malignant and malignant human breast tissues.
abstract: Links between a low vitamin D status and an increased risk of breast cancer have been observed in epidemiological studies. These links have been investigated in human tissue homogenates and cultured cell lines. We have used non-malignant, malignant and normal reduction mammoplasty breast tissues to investigate the biological and metabolic consequences of the application of vitamin D to intact ex vivo human breast tissue. Tissues were exposed to 1α,25(OH)(2)D(3) (1,25D; active metabolite) and 25(OH)D (25D; pre-metabolite). Changes in mRNA expression and protein expression after vitamin D exposure were analysed. Results indicate that while responses in normal and non-malignant breast tissues are similar between individuals, different tumour tissues are highly variable with regards to their gene expression and biological response. Collectively, malignant breast tissue responds well to active 1,25D, but not to the inactive pre-metabolite 25D. This may have consequences for the recommendation of vitamin D supplementation in breast cancer patients.
authors: Breast Cancer Genetics Group, Centre for Personalised Cancer Medicine, University of Adelaide, Australia. Rachel.Suetani@adelaide.edu.au
authors: Rachel J
authors: RJ
authors: Suetani
authors: Kristen
authors: K
authors: Ho
authors: Shalini
authors: S
authors: Jindal
authors: Jim
authors: J
authors: Manavis
authors: Paul M
authors: PM
authors: Neilsen
authors: Kathleen I
authors: KI
authors: Pishas
authors: Elisabeth
authors: E
authors: Rippy
authors: Melissa
authors: M
authors: Bochner
authors: James
authors: J
authors: Kollias
authors: P Grantley
authors: PG
authors: Gill
authors: Howard A
authors: HA
authors: Morris
authors: David F
authors: DF
authors: Callen
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002112:Calcifediol / Q000494:pharmacology / Q000502:physiology*; D002117:Calcitriol / Q000494:pharmacology / Q000502:physiology*; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019394:Ki-67 Antigen / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors; D018167:Receptors, Calcitriol / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D046509:Tissue Culture Techniques; D015854:Up-Regulation; D065668:Vitamin D3 24-Hydroxylase
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007093:Imidazoles; D019394:Ki-67 Antigen; D010879:Piperazines; D018167:Receptors, Calcitriol; C482205:nutlin 3; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; D002117:Calcitriol; D002112:Calcifediol