Thyroid Abnormalities and Hepatocellular Carcinoma in Mice Transgenic for V-erbA

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1994 Sep 15

PMID 7925269

Citations 27

Authors

C Barlow

B Meister

M Lardelli

U Lendahl

B Vennstrom

Affiliations

Soon will be listed here.

Abstract

The v-erbA oncogene consists of an avian retroviral gag gene fused to a mutated thyroid hormone receptor. To define better its role as an oncogene in mammals and its ability to function as a dominant negative transcription factor, transgenic mice expressing v-erbA ubiquitously were generated. The effects of v-erbA are pleiotropic, tissue-specific and dose dependent. Mice have breeding disorders, abnormal behavior, reduced adipose tissue, hypothyroidism with inappropriate TSH response, and enlarged seminal vesicles. This provides an animal model consistent with the proposal that v-ErbA functions as a dominant negative receptor by transcriptional interference or squelching of normal receptors or associated proteins. Finally, male animals develop hepatocellular carcinoma, demonstrating that v-erbA can promote neoplasia in mammals.

Citing Articles

Actions of thyroid hormones and thyromimetics on the liver.

Sinha R, Bruinstroop E, Yen P Nat Rev Gastroenterol Hepatol. 2024; 22(1):9-22.

PMID: 39420154 PMC: 7616774. DOI: 10.1038/s41575-024-00991-4.

Impact of Hypothyroidism on Patients with Hepatocellular Carcinoma Undergoing Liver Transplantation.

Salman A, Aon M, Hussein A, Salman M, Tourky M, Mahmoud A Int J Gen Med. 2021; 14:5711-5718.

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Thyroid hormones in diabetes, cancer, and aging.

Gauthier B, Sola-Garcia A, Caliz-Molina M, Lorenzo P, Cobo-Vuilleumier N, Capilla-Gonzalez V Aging Cell. 2020; 19(11):e13260.

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Roles of Thyroid Hormone-Associated microRNAs Affecting Oxidative Stress in Human Hepatocellular Carcinoma.

Huang P, Wang C, Yeh C, Lin K Int J Mol Sci. 2019; 20(20).

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Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis.

Liu Y, Yeh C, Lin K Int J Mol Sci. 2019; 20(20).

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References

Refetoff S, DeWIND L, DeGroot L . Familial syndrome combining deaf-mutism, stuppled epiphyses, goiter and abnormally high PBI: possible target organ refractoriness to thyroid hormone. J Clin Endocrinol Metab. 1967; 27(2):279-94. DOI: 10.1210/jcem-27-2-279. View

Ambrosino C, Cicatiello L, Cobellis G, Addeo R, Sica V, Bresciani F . Functional antagonism between the estrogen receptor and Fos in the regulation of c-fos protooncogene transcription. Mol Endocrinol. 1993; 7(11):1472-83. DOI: 10.1210/mend.7.11.8114761. View

Frykberg L, Palmieri S, Beug H, Graf T, Hayman M, Vennstrom B . Transforming capacities of avian erythroblastosis virus mutants deleted in the erbA or erbB oncogenes. Cell. 1983; 32(1):227-38. DOI: 10.1016/0092-8674(83)90513-5. View

Kahn P, Frykberg L, Brady C, Stanley I, Beug H, Vennstrom B . v-erbA cooperates with sarcoma oncogenes in leukemic cell transformation. Cell. 1986; 45(3):349-56. DOI: 10.1016/0092-8674(86)90320-x. View

Sap J, Munoz A, Damm K, Goldberg Y, Ghysdael J, Leutz A . The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986; 324(6098):635-40. DOI: 10.1038/324635a0. View

Weinberger C, Thompson C, Ong E, Lebo R, Gruol D, Evans R . The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986; 324(6098):641-6. DOI: 10.1038/324641a0. View

Gandrillon O, Jurdic P, Benchaibi M, Xiao J, Ghysdael J, Samarut J . Expression of the v-erbA oncogene in chicken embryo fibroblasts stimulates their proliferation in vitro and enhances tumor growth in vivo. Cell. 1987; 49(5):687-97. DOI: 10.1016/0092-8674(87)90545-9. View

Gunning P, Leavitt J, MUSCAT G, Ng S, Kedes L . A human beta-actin expression vector system directs high-level accumulation of antisense transcripts. Proc Natl Acad Sci U S A. 1987; 84(14):4831-5. PMC: 305199. DOI: 10.1073/pnas.84.14.4831. View

Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162(1):156-9. DOI: 10.1006/abio.1987.9999. View

10.

Jansson M, Beug H, Gray C, Graf T, Vennstrom B . Defective v-erbB genes can be complemented by v-erbA in erythroblast and fibroblast transformation. Oncogene. 1987; 1(2):167-73. View

11.

Zenke M, Kahn P, Disela C, Vennstrom B, Leutz A, Keegan K . v-erbA specifically suppresses transcription of the avian erythrocyte anion transporter (band 3) gene. Cell. 1988; 52(1):107-19. DOI: 10.1016/0092-8674(88)90535-1. View

12.

Munoz A, Zenke M, Gehring U, Sap J, Beug H, Vennstrom B . Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein. EMBO J. 1988; 7(1):155-9. PMC: 454236. DOI: 10.1002/j.1460-2075.1988.tb02795.x. View

13.

Evans R . The steroid and thyroid hormone receptor superfamily. Science. 1988; 240(4854):889-95. PMC: 6159881. DOI: 10.1126/science.3283939. View

14.

Damm K, Thompson C, Evans R . Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist. Nature. 1989; 339(6226):593-7. DOI: 10.1038/339593a0. View

15.

Sap J, Munoz A, Schmitt J, Stunnenberg H, Vennstrom B . Repression of transcription mediated at a thyroid hormone response element by the v-erb-A oncogene product. Nature. 1989; 340(6230):242-4. DOI: 10.1038/340242a0. View

16.

Forrest D, Sjoberg M, Vennstrom B . Contrasting developmental and tissue-specific expression of alpha and beta thyroid hormone receptor genes. EMBO J. 1990; 9(5):1519-28. PMC: 551844. DOI: 10.1002/j.1460-2075.1990.tb08270.x. View

17.

Sandgren E, Luetteke N, Palmiter R, Brinster R, Lee D . Overexpression of TGF alpha in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast. Cell. 1990; 61(6):1121-35. DOI: 10.1016/0092-8674(90)90075-p. View

18.

Jhappan C, Stahle C, Harkins R, Fausto N, Smith G, Merlino G . TGF alpha overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell. 1990; 61(6):1137-46. DOI: 10.1016/0092-8674(90)90076-q. View

19.

de Verneuil H, Metzger D . The lack of transcriptional activation of the v-erbA oncogene is in part due to a mutation present in the DNA binding domain of the protein. Nucleic Acids Res. 1990; 18(15):4489-97. PMC: 331269. DOI: 10.1093/nar/18.15.4489. View

20.

Glass C, Holloway J . Regulation of gene expression by the thyroid hormone receptor. Biochim Biophys Acta. 1990; 1032(2-3):157-76. DOI: 10.1016/0304-419x(90)90002-i. View