Metastasis-associated protein 1 (MTA1) and its short form (MTA1s) regulate the function of estrogen receptors (ERs). Estrogens, via ERs, affect placental growth and fetal development, a process that may involve MTA1 signaling. Expression of MTA1, MTA1s, ERα, and ERβ genes and proteins in rat placentas was studied on 16, 19, and 21 days of gestation (dg). The ERβ messenger RNA decreased significantly toward the end of gestation, whereas its protein level increased in the nuclear fraction on 21 dg. Both MTA1 and MTA1s increased with gestation. Decidual, trophoblast giant, glycogen, and villous trophoblast cells expressed MTA1, ERα, and ERβ proteins on all dg with colocalization of MTA1 with ERα and ERβ in the nucleus and cytoplasm. Expression of MTA1 suggests a possible role in regulating placental functions; considering the repressive function of MTA1 on ERs, the expression of MTA1 suggests that placental cells may be less sensitive to estrogens during late pregnancy.
FurukawaSHayashiSUsudaKAbeMHagioSOgawaI. Toxicological pathology in the rat placenta. J Toxicol Pathol. 2011;24
(2):95–111.
2.
FonsecaBMCorreia-da-SilvaGTeixeiraNA. The rat as an animal model for fetoplacental development: a reappraisal of the post-implantation period. Reprod Biol. 2012;12
(2):97–118.
3.
BartholomeuszRKBruceNWLynchAM. Embryo survival, and fetal and placental growth following elevation of maternal estradiol blood concentrations in the rat. Biol Reprod. 1999;61
(1):46–50.
4.
ManavathiBKumarR. Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin. J Cell Physiol. 2006;207
(3):594–604.
5.
Al-BaderM. Estrogen receptors alpha and beta in rat placenta: detection by RT-PCR, real time PCR and Western blotting. Reprod Biol Endocrinol. 2006;4:13.
6.
GambinoYPMaymoJLPerez PerezA. Elsevier trophoblast research award lecture: molecular mechanisms underlying estrogen functions in trophoblastic cells--focus on leptin expression. Placenta. 2012;(33 suppl): S63–S70.
ManavathiBKumarR. Metastasis tumor antigens, an emerging family of multifaceted master coregulators. J Biol Chem. 2007;282
(3):1529–1533.
9.
KumarRWangRABagheri-YarmandR. Emerging roles of MTA family members in human cancers. Semin Oncol. 2003;30
(5 suppl 16):30–37.
10.
LiWBaoWMaJ. Metastasis tumor antigen 1 is involved in the resistance to heat stress-induced testicular apoptosis. FEBS Lett. 2008;582
(6):869–873.
11.
MaoXYChenHWangH. MTA1 expression correlates significantly with ER-alpha methylation in breast cancer. Tumour Biol. 2012;33
(5):1565–1572.
12.
BruningAMakovitzkyJGingelmaierAFrieseKMylonasI. The metastasis-associated genes MTA1 and MTA3 are abundantly expressed in human placenta and chorionic carcinoma cells. Histochem Cell Biol. 2009;132
(1):33–38.
13.
LiDQPakalaSBNairSSEswaranJKumarR. Metastasis-associated protein 1/nucleosome remodeling and histone deacetylase complex in cancer. Cancer Res. 2012;72
(2):387–394.
14.
MishraSKYangZMazumdarATalukderAHLaroseLKumarR. Metastatic tumor antigen 1 short form (MTA1 s) associates with casein kinase I-gamma2, an estrogen-responsive kinase. Oncogene. 2004;23
(25):4422–4429.
15.
ChengGImamovOOmotoYWarnerMGustafssonJA. What is the value of measuring MTA-1 s in breast cancer?Mol Interv. 2002;2(6):360–362, 338.
16.
Al-BaderMAl-SajiSFordCH. Real-time PCR: detection of oestrogen receptor-alpha and -beta isoforms and variants in breast cancer. Anticancer Res. 2010;30
(10):4147–4156.
17.
YoungKHuangCLinS. Two-phased alteration and clinical relevance of MTA1 and MTA1 s gene expression: a quantitative PCR analysis in breast cancer patients. J Cancer Mol. 2006;(2):79–84.
18.
Al-BaderMDEl-AbdallahAARedzicZB. Ontogenic profile of estrogen receptor alpha and beta mRNA and protein expression in fetal rat brain. Neurosci Lett. 2008;440
(3):222–226.
19.
LivakKJSchmittgenTD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25
(4):402–408.
20.
WilsonMEFordSP. Comparative aspects of placental efficiency. Reprod Suppl. 2001;58:223–232.
21.
BukovskyACaudleMRCekanovaM. Placental expression of estrogen receptor beta and its hormone binding variant--comparison with estrogen receptor alpha and a role for estrogen receptors in asymmetric division and differentiation of estrogen-dependent cells. Reprod Biol Endocrinol. 2003;1:36.
22.
ForsterCMakelaSWarriA. Involvement of estrogen receptor beta in terminal differentiation of mammary gland epithelium. Proc Natl Acad Sci U S A. 2002;99
(24):15578–15583.
23.
BukovskyACekanovaMCaudleMR. Expression and localization of estrogen receptor-alpha protein in normal and abnormal term placentae and stimulation of trophoblast differentiation by estradiol. Reprod Biol Endocrinol. 2003;1:13.
24.
Hodges-GallagherLValentineCDEl BaderS. Estrogen receptor beta increases the efficacy of antiestrogens by effects on apoptosis and cell cycling in breast cancer cells. Breast Cancer Res Treat. 2008;109
(2):241–250.
25.
TreeckOLattrichCSpringwaldAOrtmannO. Estrogen receptor beta exerts growth-inhibitory effects on human mammary epithelial cells. Breast Cancer Res Treat. 2010;120
(3):557–565.
26.
MalassineAFrendoJLEvain-BrionD. A comparison of placental development and endocrine functions between the human and mouse model. Hum Reprod Update. 2003;9
(6):531–539.
27.
MarottiJDCollinsLCHuRTamimiRM. Estrogen receptor-beta expression in invasive breast cancer in relation to molecular phenotype: results from the Nurses’ Health Study. Mod Pathol. 2010;23
(2):197–204.
28.
MatthewsJGustafssonJA. Estrogen signaling: a subtle balance between ER alpha and ER beta. Mol Interv. 2003;3
(5):281–292.
29.
HsiaoWCChoWCLinPWLinSLLeeWYYoungKC. Quantitative profile of estrogen receptor variants/isoforms in Taiwanese women with breast cancer. Eur J Surg Oncol. 2006;32
(5):492–497.
30.
MoonWSChangKTarnawskiAS. Overexpression of metastatic tumor antigen 1 in hepatocellular carcinoma: Relationship to vascular invasion and estrogen receptor-alpha. Hum Pathol. 2004;35
(4):424–429.
CouseJFKorachKS. Contrasting phenotypes in reproductive tissues of female estrogen receptor null mice. Ann N Y Acad Sci. 2001;948:1–8.
33.
LiDQOhshiroKKhanMNKumarR. Requirement of MTA1 in ATR-mediated DNA damage checkpoint function. J Biol Chem. 2010;285
(25):19802–19812.
34.
CuiYNiuAPestellR. Metastasis-associated protein 2 is a repressor of estrogen receptor alpha whose overexpression leads to estrogen-independent growth of human breast cancer cells. Mol Endocrinol. 2006;20
(9):2020–2035.
