title: Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27.
abstract: Heat shock protein 27 (hsp-27) is a regulator of oestrogen receptor (ER) expression and a modulator of intracellular homeostasis. In this laboratory, Shaaban et al demonstrated the importance of ER-alpha, together with Ki67, in enhancing the progression of benign breast lesions of defined morphological types. To better understand the mechanisms by which ER-alpha promotes breast neoplasia, this study was performed to test the hypothesis that the roles of ER-alpha and hsp-27 may be defined by their quantitative expression in proliferative breast lesions of varying histological risk. The expression of hsp-27 was identified using a specific monoclonal antibody and analysed to assess the proportion of positive epithelial cells using digitised morphometric image analysis. The expression of ER-alpha was analysed by immunohistochemistry and Western blotting in a variety of benign (HUMA121) and malignant mammary cell lines, including ER-alpha(+) (MCF7, ZR-75, T47D) and ER-alpha(-) (MDA-MB 231) breast cancer cell lines. The data confirm that, during progression from normal through proliferative breast lesions to in situ cancer, there was a significant increase in both the proportion and the optical density of the epithelial cells expressing hsp-27. The mean levels of expression ranged from 7.4% of the total number of epithelial cells in normal lobules to 25.17% of epithelial cells in hyperplasias of usual type (HUT) to 61.1% of epithelial cells in ductal carcinoma in situ (P<0.001). The study has confirmed the expression of hsp-27 to be closely associated with ER-alpha(+) expression, and that its regulated expression occurs early along the mammary oncogenic pathway, supporting the initial hypothesis. It is our proposal that the differential expression of hsp-27 modulates the phenotypic behaviour of morphologically benign epithelial cells and hence may be an important determinant in initiating, or promoting, a population of human mammary cancers.
authors.affiliation: Clatterbridge Cancer Research Trust, JK Douglas Laboratories, Bebington, Wirral CH63 4JY, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: O'Neill
authors.forename: A M
authors.initials: AM
authors.lastname: Shaaban
authors.forename: C R
authors.initials: CR
authors.lastname: West
authors.forename: A
authors.initials: A
authors.lastname: Dodson
authors.forename: C
authors.initials: C
authors.lastname: Jarvis
authors.forename: P
authors.initials: P
authors.lastname: Moore
authors.forename: M P A
authors.initials: MP
authors.lastname: Davies
authors.forename: D R
authors.initials: DR
authors.lastname: Sibson
authors.forename: C S
authors.initials: CS
authors.lastname: Foster
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001941:Breast Diseases / Q000235:genetics* / Q000503:physiopathology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D002471:Cell Transformation, Neoplastic; D004847:Epithelial Cells / Q000502:physiology; D047628:Estrogen Receptor alpha; D005260:Female; D006360:Heat-Shock Proteins / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D010641:Phenotype; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000502:physiology; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D047628:Estrogen Receptor alpha; D006360:Heat-Shock Proteins; D011960:Receptors, Estrogen