Brn-3b transcription factor in breast tumourigenesis: regulation of genes associated with growth and migration of cancer cells

Excerpt

The Brn-3b transcription factor is elevated in many breast cancers compared with levels found in normal breast epithelial cells. High levels of Brn-3b increase growth and proliferation of cancer cells, both in vitro and in vivo, but also alter migration and confer resistance to growth inhibitory stimulus [1]. Conversely, low levels of Brn-3b slow the growth of these cells. As a transcription factor, Brn3b changes the growth and behaviour of breast cancer cells by modifying the expression of target genes, either directly or indirectly upon association with the proliferation-associated estrogen receptor (ER) [2]. A number of Brn-3b target genes have been identified that alter the growth and behaviour of these cancer cells. For instance, Brn-3b transactivates the promoter of the cyclin-dependent kinase, CDK4 [3], that is required for cell cycle progression and hence proliferation. Brn-3b also represses the promoter of the tumour suppressor gene, BRCA1, and inversely correlates with BRCA1 protein in tumour biopsies. We have recently demonstrated that the small heat shock protein, HSP27, is also regulated by Brn-3b [4]. High expression of HSP27 in breast cancers is associated with increased anchorage-independent growth, increased invasiveness and resistance to chemotherapeutic drugs and poor prognosis. Thus, in cancers expressing high levels of Brn-3b the downstream target genes regulated by this transcription factor can alter the growth and behaviour of these cells. …