The T-box transcription factors TBX2 and TBX3 in mammary gland development and breast cancer - PubMed (original) (raw)

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The T-box transcription factors TBX2 and TBX3 in mammary gland development and breast cancer

Nataki C Douglas et al. J Mammary Gland Biol Neoplasia. 2013 Jun.

Abstract

TBX2 and TBX3, closely related members of the T-box family of transcription factor genes, are expressed in mammary tissue in both humans and mice. Ulnar mammary syndrome (UMS), an autosomal dominant disorder caused by mutations in TBX3, underscores the importance of TBX3 in human breast development, while abnormal mammary gland development in Tbx2 or Tbx3 mutant mice provides models for experimental investigation. In addition to their roles in mammary development, aberrant expression of TBX2 and TBX3 is associated with breast cancer. TBX2 is preferentially amplified in BRCA1/2-associated breast cancers and TBX3 overexpression has been associated with advanced stage disease and estrogen-receptor-positive breast tumors. The regulation of Tbx2 and Tbx3 and the downstream targets of these genes in development and disease are not as yet fully elucidated. However, it is clear that the two genes play unique, context-dependent roles both in mammary gland development and in mammary tumorigenesis.

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Figures

Figure 1

Figure 1

Expression of Tbx2 and Tbx3 in the developing mammary gland and the effect of heterozygosity for a mutation in Tbx3. A–D. Whole mount in situ hybridization for Tbx2 and Tbx3 at embryonic day (E) 10.5 and E11.5 shows expression of both genes in the mammary line between the forelimb and hindlimb and Tbx3 expression in the mammary placodes when they first appear (arrowheads). E, F. Skin and mammary gland preparation from late gestation embryos stained with Carmine’s Alum to show the nipple and ductal tree, which is reduced in Tbx3 heterozygotes. G, H. Mammary gland preparations from 8 week old virgin females stained with Carmine’s Alum showing a reduction in the branching network of Tbx3 heterozygotes. (Modified with permission from [7]).

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