Details

Autor(en) / Beteiligte

• LEE, Sonia A
• NDISANG, Daniel
• BUDHRAM-MAHADEO, Vishwanie S
• PATEL, Chandrakant
• DENNIS, Jonathan H
• FAULKES, David J
• D'ARRIGO, Corrado
• SAMADY, Laila
• FAROOQUI-KABIR, Saleha
• HEADS, Richard J
• LATCHMAN, David S

Titel

Expression of the Brn-3b transcription factor correlates with expression of HSP-27 in breast cancer biopsies and is required for maximal activation of the HSP-27 promoter

Ist Teil von

• Cancer research (Chicago, Ill.), 2005-04, Vol.65 (8), p.3072-3080

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• In breast cancer, overexpression of the small heat shock protein, HSP-27, is associated with increased anchorage-independent growth, increased invasiveness, and resistance to chemotherapeutic drugs and is associated with poor prognosis and reduced disease-free survival. Therefore, factors that increase the expression of HSP-27 in breast cancer are likely to affect the prognosis and outcome of treatment. In this study, we show a strong correlation between elevated levels of the Brn-3b POU transcription factor and high levels of HSP-27 protein in manipulated MCF-7 breast cancer cells as well as in human breast biopsies. Conversely, HSP-27 is decreased on loss of Brn-3b. In cotransfection assays, Brn-3b can strongly transactivate the HSP-27 promoter, supporting a role for direct regulation of HSP-27 expression. Brn-3b also cooperates with the estrogen receptor (ER) to facilitate maximal stimulation of the HSP-27 promoter, with significantly enhanced activity of this promoter observed on coexpression of Brn-3b and ER compared with either alone. RNA interference and site-directed mutagenesis support the requirement for the Brn-3b binding site on the HSP-27 promoter, which facilitates maximal transactivation either alone or on interaction with the ER. Chromatin immunoprecipitation provides evidence for association of Brn-3b with the HSP-27 promoter in the intact cell. Thus, Brn-3b can, directly and indirectly (via interaction with the ER), activate HSP-27 expression, and this may represent one mechanism by which Brn-3b mediates its effects in breast cancer cells.