Please use this identifier to cite or link to this item:
Title: Actin alpha cardiac muscle 1 gene expression is upregulated in the skeletal muscle of men undergoing androgen deprivation therapy for prostate cancer.
Austin Authors: Cheung, Ada S ;de Rooy, Casey;Levinger, Itamar ;Rana, Kesha;Clarke, Michele V;How, Jackie M Y;Garnham, Andrew;McLean, Catriona;Zajac, Jeffrey D ;Davey, Rachel A;Grossmann, Mathis 
Affiliation: Department of Pathology, Alfred Health, Victoria, Australia
Medicine (University of Melbourne)
Institute of Sport, Exercise, and Active Living (ISEAL), Victoria University, Victoria, Australia
Australian Institute for Musculoskeletal Science (AIMSS), Western Health, St. Albans, Victoria, Australia
Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
Issue Date: Nov-2017
Date: 2017-07-27
Publication information: The Journal of Steroid Biochemistry and Molecular Biology 2017; 174: 56-64
Abstract: Androgen deprivation therapy (ADT) decreases muscle mass and function but no human studies have investigated the underlying genetic or cellular effects. We tested the hypothesis that ADT will lead to changes in skeletal muscle gene expression, which may explain the adverse muscle phenotype seen clinically. We conducted a prospective cohort study of 9 men with localised prostate cancer who underwent a vastus lateralis biopsy before and after 4 weeks of ADT. Next-generation RNA sequencing was performed and genes differentially expressed following ADT underwent gene ontology mining using Ingenuity Pathway Analysis. Differential expression of genes of interest was confirmed by quantitative PCR (Q-PCR) on gastrocnemius muscle of orchidectomised mice and sham controls (n=11/group). We found that in men, circulating total testosterone decreased from 16.5±4.3nmol/L at baseline to 0.4±0.15nmol/L post-ADT (p<0.001). RNA sequencing identified 19 differentially expressed genes post-ADT (all p<0.05 after adjusting for multiple testing). Gene ontology mining identified 8 genes to be of particular interest due to known roles in androgen-mediated signalling; ABCG1, ACTC1, ANKRD1, DMPK, THY1, DCLK1, CST3 were upregulated and SLC38A3 was downregulated post-ADT. Q-PCR in mouse gastrocnemius muscle confirmed that only one gene, Actc1 was concordantly upregulated (p<0.01) in orchidectomised mice compared with controls. In conclusion, given that ACTC1 upregulation is associated with improved muscle function in certain myopathies, we hypothesise that upregulation of ACTC1 may represent a compensatory response to ADT-induced muscle loss. Further studies will be required to evaluate the role and function of ACTC1.
DOI: 10.1016/j.jsbmb.2017.07.029
ORCID: 0000-0001-5257-5525
Journal: The Journal of Steroid Biochemistry and Molecular Biology
PubMed URL: 28756295
Type: Journal Article
Subjects: Androgens
Prostatic neoplasms
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on May 18, 2024

Google ScholarTM


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