Skip navigation
Skip navigation

The SuprMam1 breast cancer susceptibility locus disrupts the vitamin D/ calcium/ parathyroid hormone pathway and alters bone structure in congenic mice

Ratnadiwakara, Madara; Rooke, Melissa; Ohms, Stephen; French, Hugh; Williams, Rohan; Li, Rachel; Zhang, Daohai; Lucas, Robyn; Blackburn, Anneke

Description

Breast cancer is a complex disease, and approximately 30% of cases are considered to be hereditary or familial, with a large fraction of this being polygenic. However, it is difficult to demonstrate the functional importance of genes of small effect in population studies, and these genes are not always easily targeted for prevention. The SuprMam (suppressor of mammary tumour) breast cancer susceptibility alleles were previously identified as contributors to spontaneous mammary tumour...[Show more]

dc.contributor.authorRatnadiwakara, Madara
dc.contributor.authorRooke, Melissa
dc.contributor.authorOhms, Stephen
dc.contributor.authorFrench, Hugh
dc.contributor.authorWilliams, Rohan
dc.contributor.authorLi, Rachel
dc.contributor.authorZhang, Daohai
dc.contributor.authorLucas, Robyn
dc.contributor.authorBlackburn, Anneke
dc.date.accessioned2019-09-30T01:03:56Z
dc.identifier.issn0960-0760
dc.identifier.urihttp://hdl.handle.net/1885/172048
dc.description.abstractBreast cancer is a complex disease, and approximately 30% of cases are considered to be hereditary or familial, with a large fraction of this being polygenic. However, it is difficult to demonstrate the functional importance of genes of small effect in population studies, and these genes are not always easily targeted for prevention. The SuprMam (suppressor of mammary tumour) breast cancer susceptibility alleles were previously identified as contributors to spontaneous mammary tumour development in Trp53+/− mice. In this study, we have generated and characterised congenic mice that contain the BALB/c SuprMam1 (susceptibility) locus on a C57BL/6 (resistant) background and discovered a subtle impairment in the vitamin D/ calcium/ parathyroid hormone (PTH) pathway. This was evident as altered gene expression in the mammary glands of key players in this pathway. Further functional analysis of the mice revealed elevated PTH levels, reduced Cyp27b1 expression in kidneys, and reduced trabecular bone volume/ tissue volume percentage. Plasma 25(OH)D and serum calcium were unchanged. This impairment was a result of genetic differences and occurred only in females, but the elevated PTH levels could be overcome with either calcium or vitamin D dietary supplementation. Either low levels of active vitamin D (1,25(OH)2D) or chronically elevated PTH levels may contribute to increased breast cancer susceptibility. These indicators are not easily measured in human population studies, but either mechanism may be preventable with dietary calcium or vitamin D supplements. Therefore, SuprMam congenic mice could serve as a valuable model for studying the role of gene-hormone-environment interactions of the vitamin D/ calcium/ PTH pathway in cancer and other diseases and for testing preventive interventions.
dc.format.mimetypeapplication/pdf
dc.language.isoen_AU
dc.publisherPergamon Press
dc.rights© 2018 Elsevier Ltd
dc.sourceJournal of Steroid Biochemistry and Molecular Biology
dc.titleThe SuprMam1 breast cancer susceptibility locus disrupts the vitamin D/ calcium/ parathyroid hormone pathway and alters bone structure in congenic mice
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume188
dc.date.issued2019
local.identifier.absfor111716 - Preventive Medicine
local.identifier.absfor110306 - Endocrinology
local.identifier.absfor111203 - Cancer Genetics
local.identifier.ariespublicationu1042365xPUB36
local.publisher.urlhttps://www.elsevier.com/en-au
local.type.statusPublished Version
local.contributor.affiliationRatnadiwakara, Madara, Administrative Division, ANU
local.contributor.affiliationRooke, Melissa, College of Health and Medicine, ANU
local.contributor.affiliationOhms, Stephen J, College of Health and Medicine, ANU
local.contributor.affiliationFrench, Hugh, College of Health and Medicine, ANU
local.contributor.affiliationWilliams, Rohan, College of Health and Medicine, ANU
local.contributor.affiliationLi, Rachel, College of Health and Medicine, ANU
local.contributor.affiliationZhang, Daohai, College of Health and Medicine, ANU
local.contributor.affiliationLucas, Robyn, College of Health and Medicine, ANU
local.contributor.affiliationBlackburn, Anneke, College of Health and Medicine, ANU
local.description.embargo2037-12-31
dc.relationhttp://purl.org/au-research/grants/nhmrc/179842
dc.relationhttp://purl.org/au-research/grants/nhmrc/366787
local.bibliographicCitation.startpage48
local.bibliographicCitation.lastpage58
local.identifier.doi10.1016/j.jsbmb.2018.12.004
local.identifier.absseo920106 - Endocrine Organs and Diseases (excl. Diabetes)
local.identifier.absseo920113 - Oro-Dental Disorders
local.identifier.absseo920102 - Cancer and Related Disorders
dc.date.updated2019-04-21T08:24:13Z
local.identifier.scopusID2-s2.0-85059187258
CollectionsANU Research Publications

Download

File Description SizeFormat Image
01_Ratnadiwakara_The_SuprMam1_breast_cancer_2019.pdf2.67 MBAdobe PDF    Request a copy


Items in Open Research are protected by copyright, with all rights reserved, unless otherwise indicated.

Updated:  19 May 2020/ Responsible Officer:  University Librarian/ Page Contact:  Library Systems & Web Coordinator