Expression analysis of E-cadherin, Slug and GSK3beta in invasive ductal carcinoma of breast.
BACKGROUND
Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-beta and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/beta-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast.


METHODS
In the current study, we analyzed the expression patterns and relationships between the key Wnt/beta-catenin signaling components- E-cadherin, Slug and GSK3beta in IDCs of breast.


RESULTS
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 GSK3beta expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3beta. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear beta-catenin (p = 0.001), and cytoplasmic beta-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/beta-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3beta nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression.


CONCLUSIONS
The present study for the first time provided the clinical evidence in support of Wnt/beta-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3beta with beta-catenin in implementing EMT in these cells.
Prasad
Chandra P
CP
Department of Anatomy, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India. researchchandra@gmail.com
Rath
Gayatri
G
Mathur
Sandeep
S
Bhatnagar
Dinesh
D
Parshad
Rajinder
R
Ralhan
Ranju
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D008875:Middle Aged; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D051155:Wnt1 Protein / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051155:Wnt1 Protein; D051176:beta Catenin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3