Expression analysis of E-cadherin, Slug and GSK3β in invasive ductal carcinoma of breast
1 Department of Anatomy, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
2 Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
3 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
4 Department of Surgery, Vardhman Mahavir Medical College and Safdarjung Hospital, New Dehi, India
5 Department of Surgery, All India Institute of Medical Sciences; New Delhi -110029, India
6 Sonshine Family Centre for Head & Neck Disease, Mount Sinai Hospital, 600 University Avenue, Room 6-500, Toronto, Ontario M5G 1X5, Canada
7 Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, 600 University Avenue, Room 6-500, Toronto, Ontario M5G 1X5, Canada
8 Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Room 6-500, Toronto, Ontario M5G 1X5, Canada
9 Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, M5G 2N2, Canada
BMC Cancer 2009, 9:325 doi:10.1186/1471-2407-9-325Published: 14 September 2009
Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-β and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/β-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast.
In the current study, we analyzed the expression patterns and relationships between the key Wnt/β-catenin signaling components- E-cadherin, Slug and GSK3β in IDCs of breast.
Of the 98 IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs examined. Loss or reduced level of cytoplasmic GSK3β expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3β. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear β-catenin (p = 0.001), and cytoplasmic β-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/β-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3β nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression.
The present study for the first time provided the clinical evidence in support of Wnt/β-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3β with β-catenin in implementing EMT in these cells.