Biallelic inactivation of the thyroid hormone receptor β1 gene in early stage breast cancer

Zheng Li, Zhen Hang Meng, Raman Chandrasekaran, Wen Lin Kuo, Colin C. Collins, Joe Gray, Shanaz H. Dairkee

Research output: Contribution to journalArticle

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Abstract

Loss of heterozygosity within the short arm of chromosome 3 is a common molecular event in several types of solid tumors. In breast cancer, 3p loss of heterozygosity occurs in invasive tumor cells as well as in morphologically normal terminal ductal lobular units adjacent to carcinoma in some cases [G. Deng et al, Science (Wash. DC), 274: 2057-2059, 1996.]. The most frequent region of allelic loss at 3p24.3 in morphologically normal terminal ductal lobular units encompasses the thyroid hormone receptor β1 (TRβ1) gene. Here we have observed a variable degree of TRβ1 promoter hypermethylation in all 11 cases of primary breast cancer examined. Moreover, hypermethylation occurred at the same CpG sites in nonmalignant tissue peripheral to carcinoma in 4 of 11 cases. The lack of TRβ1 nuclear staining, a likely result of biallelic gene inactivation, was observed in 25% (22 of 85) of primary tumors. This is a first demonstration of promoter hypermethylation and a concurrent reduction of TRβ1 transcripts in breast cancer cell lines, although specific CpG sites targeted for gene silencing remain to be determined. Gene expression was restored by treatment with 5-aza-deoxycytidine in such cases. The observation of early, frequent, and multiple mechanisms of TRβ1 inactivation suggests a potential role for this gene in the suppression of breast tumorigenesis.

Original languageEnglish (US)
Pages (from-to)1939-1943
Number of pages5
JournalCancer Research
Volume62
Issue number7
StatePublished - Apr 1 2002
Externally publishedYes

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Thyroid Hormone Receptors
Breast Neoplasms
Loss of Heterozygosity
Genes
Gene Silencing
Carcinoma
Neoplasms
Deoxycytidine
Chromosomes, Human, Pair 3
Carcinogenesis
Breast
Observation
Staining and Labeling
Gene Expression
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Li, Z., Meng, Z. H., Chandrasekaran, R., Kuo, W. L., Collins, C. C., Gray, J., & Dairkee, S. H. (2002). Biallelic inactivation of the thyroid hormone receptor β1 gene in early stage breast cancer. Cancer Research, 62(7), 1939-1943.

Biallelic inactivation of the thyroid hormone receptor β1 gene in early stage breast cancer. / Li, Zheng; Meng, Zhen Hang; Chandrasekaran, Raman; Kuo, Wen Lin; Collins, Colin C.; Gray, Joe; Dairkee, Shanaz H.

In: Cancer Research, Vol. 62, No. 7, 01.04.2002, p. 1939-1943.

Research output: Contribution to journalArticle

Li, Z, Meng, ZH, Chandrasekaran, R, Kuo, WL, Collins, CC, Gray, J & Dairkee, SH 2002, 'Biallelic inactivation of the thyroid hormone receptor β1 gene in early stage breast cancer', Cancer Research, vol. 62, no. 7, pp. 1939-1943.
Li Z, Meng ZH, Chandrasekaran R, Kuo WL, Collins CC, Gray J et al. Biallelic inactivation of the thyroid hormone receptor β1 gene in early stage breast cancer. Cancer Research. 2002 Apr 1;62(7):1939-1943.
Li, Zheng ; Meng, Zhen Hang ; Chandrasekaran, Raman ; Kuo, Wen Lin ; Collins, Colin C. ; Gray, Joe ; Dairkee, Shanaz H. / Biallelic inactivation of the thyroid hormone receptor β1 gene in early stage breast cancer. In: Cancer Research. 2002 ; Vol. 62, No. 7. pp. 1939-1943.
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