Tetratricopeptide repeat domain 9A negatively regulates estrogen receptor alpha activity

International Journal of Biological Sciences
Smeeta ShresthaValerie C L Lin

Abstract

Tetratricopeptide repeat domain 9A (TTC9A) is a target gene of estrogen and progesterone. It is over-expressed in breast cancer. However, little is known about the physiological function of TTC9A. The objectives of this study were to establish a Ttc9a knockout mouse model and to study the consequence of Ttc9a gene inactivation. The Ttc9a targeting vector was generated by replacing the Ttc9a exon 1 with a neomycin cassette. The mice homozygous for Ttc9a exon 1 deletion appear to grow normally and are fertile. However, further characterization of the female mice revealed that Ttc9a deficiency is associated with greater body weight, bigger thymus and better mammary development in post-pubertal mice. Furthermore, Ttc9a deficient mammary gland was more responsive to estrogen treatment with greater mammary ductal lengthening, ductal branching and estrogen target gene induction. Since Ttc9a is induced by estrogen in estrogen target tissues, these results suggest that Ttc9a is a negative regulator of estrogen function through a negative feedback mechanism. This is supported by in vitro evidence that TTC9A over-expression attenuated ERα activity in MCF-7 cells. Although TTC9A does not bind to ERα or its chaperone protein Hsp90 directly,...Continue Reading

Citations

Oct 28, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lauren OsborneZachary Kaminsky
Aug 8, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Anthony S ZannasElisabeth B Binder
Nov 22, 2016·Scientific Reports·Lee Wei LimValerie Chun Ling Lin
Dec 30, 2016·Cancer Science·Miho TakaokaAkira Nakanishi
Sep 30, 2018·Journal of Medical Virology·Shan-Shan XuHua Rao
May 18, 2021·Neurobiology of Stress·Olga Y Ponomareva, Kerry J Ressler
Dec 18, 2019·Psychiatry Research·Jennifer L PayneZachary A Kaminsky

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Methods Mentioned

BETA
Knockout
biopsies
genotyping
PCR
protein assay
electrophoresis
transfection
Co-IP
pull-down
co-immunoprecipitation

Software Mentioned

AxioVision
Image J

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