Silencing of Wnt Signaling and Activation of Multiple Metabolic Pathways in Response to Thyroid Hormone-stimulated Cell Proliferation

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2001 Sep 5

PMID 11533250

Citations 25

Authors

L D Miller

K S Park

Q M Guo

N W Alkharouf

R L Malek

N H Lee

E T Liu

S Y Cheng

Affiliations

Soon will be listed here.

Abstract

To investigate the transcriptional program underlying thyroid hormone (T3)-induced cell proliferation, cDNA microarrays were used to survey the temporal expression profiles of 4,400 genes. Of 358 responsive genes identified, 88% had not previously been reported to be transcriptionally or functionally modulated by T3. Partitioning the genes into functional classes revealed the activation of multiple pathways, including glucose metabolism, biosynthesis, transcriptional regulation, protein degradation, and detoxification in T3-induced cell proliferation. Clustering the genes by temporal expression patterns provided further insight into the dynamics of T3 response pathways. Of particular significance was the finding that T3 rapidly repressed the expression of key regulators of the Wnt signaling pathway and suppressed the transcriptional downstream elements of the beta-catenin-T-cell factor complex. This was confirmed biochemically, as beta-catenin protein levels also decreased, leading to a decrease in the transcriptional activity of a beta-catenin-responsive promoter. These results indicate that T3-induced cell proliferation is accompanied by a complex coordinated transcriptional reprogramming of many genes in different pathways and that early silencing of the Wnt pathway may be critical to this event.

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References

Madeira M, Paula-Barbosa M . Reorganization of mossy fiber synapses in male and female hypothyroid rats: a stereological study. J Comp Neurol. 1993; 337(2):334-52. DOI: 10.1002/cne.903370213. View

Nunez J, Couchie D, Aniello F, Bridoux A . Thyroid hormone effects on neuronal differentiation during brain development. Acta Med Austriaca. 1992; 19 Suppl 1:36-9. View

Videla L, Fernandez V . Thyroid calorigenesis and oxidative stress: modification of the respiratory burst activity in polymorphonuclear leukocytes. Braz J Med Biol Res. 1994; 27(10):2331-42. View

Lee N, Weinstock K, Kirkness E, Fuldner R, Marmaros S, Glodek A . Comparative expressed-sequence-tag analysis of differential gene expression profiles in PC-12 cells before and after nerve growth factor treatment. Proc Natl Acad Sci U S A. 1995; 92(18):8303-7. PMC: 41145. DOI: 10.1073/pnas.92.18.8303. View

Bernal J, Nunez J . Thyroid hormones and brain development. Eur J Endocrinol. 1995; 133(4):390-8. DOI: 10.1530/eje.0.1330390. View

Inomata M, Ochiai A, Akimoto S, Kitano S, Hirohashi S . Alteration of beta-catenin expression in colonic epithelial cells of familial adenomatous polyposis patients. Cancer Res. 1996; 56(9):2213-7. View

Neveu I, Arenas E . Neurotrophins promote the survival and development of neurons in the cerebellum of hypothyroid rats in vivo. J Cell Biol. 1996; 133(3):631-46. PMC: 2120825. DOI: 10.1083/jcb.133.3.631. View

Lin K, Zhu X, Shieh H, Hsu H, Chen S, McPhie P . Identification of naturally occurring dominant negative mutants of thyroid hormone alpha 1 and beta 1 receptors in a human hepatocellular carcinoma cell line. Endocrinology. 1996; 137(10):4073-81. DOI: 10.1210/endo.137.10.8828459. View

Calza L, Giardino L, Aloe L . Thyroid hormone regulates NGF content and p75LNGFR expression in the basal forebrain of adult rats. Exp Neurol. 1997; 143(2):196-206. DOI: 10.1006/exnr.1996.6361. View

10.

Korinek V, Barker N, Morin P, van Wichen D, de Weger R, Kinzler K . Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science. 1997; 275(5307):1784-7. DOI: 10.1126/science.275.5307.1784. View

11.

Morin P, Sparks A, Korinek V, Barker N, Clevers H, Vogelstein B . Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997; 275(5307):1787-90. DOI: 10.1126/science.275.5307.1787. View

12.

Wong R, Vasilyev V, Ting Y, Kutler D, Willingham M, Weintraub B . Transgenic mice bearing a human mutant thyroid hormone beta 1 receptor manifest thyroid function anomalies, weight reduction, and hyperactivity. Mol Med. 1997; 3(5):303-14. PMC: 2230075. View

13.

Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek T, Perry 3rd W . The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell. 1997; 90(1):181-92. DOI: 10.1016/s0092-8674(00)80324-4. View

14.

DeRisi J, Iyer V, Brown P . Exploring the metabolic and genetic control of gene expression on a genomic scale. Science. 1997; 278(5338):680-6. DOI: 10.1126/science.278.5338.680. View

15.

Lin K, Zhu X, Hsu H, Chen S, Shieh H, Chen S . Dominant negative activity of mutant thyroid hormone alpha1 receptors from patients with hepatocellular carcinoma. Endocrinology. 1997; 138(12):5308-15. DOI: 10.1210/endo.138.12.5625. View

16.

LUCAS F, Salinas P . WNT-7a induces axonal remodeling and increases synapsin I levels in cerebellar neurons. Dev Biol. 1998; 192(1):31-44. DOI: 10.1006/dbio.1997.8734. View

17.

Calza L, Giardino L, Aloe L . NGF content and expression in the rat pituitary gland and regulation by thyroid hormone. Brain Res Mol Brain Res. 1998; 51(1-2):60-8. DOI: 10.1016/s0169-328x(97)00213-1. View

18.

LUCAS F, Goold R, Gordon-Weeks P, Salinas P . Inhibition of GSK-3beta leading to the loss of phosphorylated MAP-1B is an early event in axonal remodelling induced by WNT-7a or lithium. J Cell Sci. 1998; 111 ( Pt 10):1351-61. DOI: 10.1242/jcs.111.10.1351. View

19.

He T, Sparks A, Rago C, Hermeking H, Zawel L, DA COSTA L . Identification of c-MYC as a target of the APC pathway. Science. 1998; 281(5382):1509-12. DOI: 10.1126/science.281.5382.1509. View

20.

Zhan Q, Wong R, Cheng S . Thyroid hormone receptor is a negative regulator in p53-mediated signaling pathways. DNA Cell Biol. 1998; 17(9):743-50. DOI: 10.1089/dna.1998.17.743. View