Down-regulation of Hsp27 (HSPB1) in MCF-7 human breast cancer cells induces upregulation of PTEN.

NIUBYS CAYADO-GUTIÉRREZ; VERA L. MONCALERO; ELIANA M. ROSALES; WALTER BERÓN; EDGARDO E. SALVATIERRA; DAIANA ALVAREZ OLMEDO; MARTÍN RADRIZZANI; DANIEL R. CIOCCA

CELL STRESS & CHAPERONES.

SPRINGER

Lugar: Dordrecht; Año: 2012 vol. 18 p. 243 - 249

1355-8145

Hsp27 (HSPB1) is usually over-expressed in breast cancers affecting the diseaseoutcome and the sensitivity of tumors to chemotherapy and radiotherapy. Hsp27interacts with other proteins such as beta-catenin, histone deacetylase HDAC6,transcription factor STAT2 and procaspase-3. Phosphatase and tensin homologue(PTEN) is a tumor suppressor gene that is deleted in many human tumors. ThePI3K/Akt signaling pathway is negatively regulated by PTEN. Hsp27 is described as akey component of the Akt signaling cascade: Akt, BAD, FKHR, Hsp27, mitogenactivatedprotein (MAP) kinase kinase-3 and -6 (MKK3/6). Here we have examinedwhether the down-regulation of Hsp27 by siHsp27 affects the PTEN levels in the MCF-7 human breast cancer cell line. PTEN was detected with two different antibodies usingwestern blots and immunocytochemistry. p-Akt was also evaluated by western blot. Inaddition, Hsp27 and PTEN were immunoprecipitated to know whether these proteinsinteract. Intracellular co-localization studies were carried out by confocal microscopy. Asignificant reduction in the Hsp27 levels was noted in the siHsp27 transfected cells.These Hsp27 down-regulated cells showed a significant increased expression of PTEN.The MW 76 kDa and 55 kDa PTEN forms were up-regulated as revealed by twodifferent antibodies. The phosphatase activity of PTEN seems to be active because p-Akt levels were reduced. Hsp27 immunoprecipitation was bringing PTEN and viceversa, these two proteins seem to interact at cytoplasmic level by FRET. Downregulationof Hsp27 stabilized PTEN protein levels. CHIP levels were not significantlyinfluenced by Hsp27 down-regulation. In conclusion, we report a novel function ofHsp27 modulating the PTEN levels in human breast cancer cells suggesting aninteraction between these two molecules.