Altered expression of anti-apoptotic proteins in non-involved tissue from cancer-containing breasts

Abstract

In a previous investigation reduced apoptosis was identified in normal breast tissue from cancer-containing breasts away from the cancer in comparison to age-matched normal breast from women without cancer. The hypothesis for this study was that defects in expression of apoptotic regulatory and DNA repair proteins would facilitate persistence of genetic alterations and predispose to breast cancer development.Using immunohistochemistry normal breast from 120 age-matched women (58 with breast cancer, 62 without) was analysed for proliferation, apoptosis, bcl2, BAX, caspase 3, Hsp27, Hsp70, BRCA1, ATM and BARD1. All assessments were performed without knowledge as to whether it was a cancer case or control. A significant difference was found for apoptotic index which was higher in controls p<0.02). There was no change in apoptotic and proliferation index with age for cancer cases unlike controls. Higher expression of bcl2 (p=0.001) and Hsp27 (p=0.001) in was found in normal breast from cancer-containing breast in comparison to controls. There were no differences in the other proteins.Apoptosis has been found to be reduced in normal breast in a separate cohort of women with breast cancer, along with increased expression of the anti-apoptotic proteins bcl2 and Hsp27.These alterations in apoptotic regulation would enhance tumour development. Further studies are needed to examine the value of these proteins as risk markers.

Analysis of CD40 expression in breast cancer and its relation to clinicopathological characteristics.

“…38,39]. Normal breast tissue from healthy women shows lower expression of Bcl-2 protein than normal breast tissue in women with cancer and in cancer tissue [40]. In breast carcinoma, Bcl-2 has been described as an independent prognostic and predictive marker [41,42,43] and loss of its expression in high risk breast carcinoma has been related to increased overall mortality, distinct metastasis and locoregional recurrence [44].…”

RP101 (brivudine) binds to heat shock protein HSP27 (HSPB1) and enhances survival in animals and pancreatic cancer patients

“…HSPB1 regulates apoptosis through its interaction with Pro-CASP3 (Rocchi et al 2006;Batchelder et al 2009), AKT1 (Rane et al 2003), and CYC1 (Pandey et al 2000). According to Rane et al (2003), disruption of the interaction between HSPB1 and AKT1 impairs AKT1 activation, leading to an enhanced rate of apoptosis.…”

“…It regulates apoptosis through interaction with STAT3 (Song et al 2004;Hsieh et al 2005;Rocchi et al 2005;Lee et al 2008), CYC1 (Cytochrome c-1) (Pandey et al 2000), and CASP3 (Caspase 3) (Rocchi et al 2006;Batchelder et al 2009). It has been suggested that the anti-apoptotic eVect of HSPB1 overexpression is associated with altered DNA topoisomerase II expression (Hansen et al 1999).…”

Cytoprotective Effect of Heat Shock Protein 27 Against Lipopolysaccharide-Induced Apoptosis of Renal Epithelial HK-2 Cells

“…Intracellular expression of Hsp27 modulates the ability of cells to respond to several types of injury, including heat shock, oxidative stress and chemical stress in order to offset the deleterious effects of cellular stresses [10,11]. Hsp27 has also been identified as an antiapoptotic factor which confers a survival advantage to cells by reduction of apoptosis [12,13]. Diagnostic test study has indicated Hsp27 is a sensitive biomarker for detection of early AKI in critically ill patients [14].…”