E-cadherin and vitamin D receptor regulation by SNAIL and ZEB1 in colon cancer: clinicopathological correlations.
E-cadherin (CDH1) gene expression is strictly regulated. The transcriptional factors SNAIL and ZEB1 are involved in its repression, whereas activation of vitamin D receptor (VDR) by vitamin D induces its transcription. We study the expression and functional correlation of SNAIL, CDH1, VDR and ZEB1 genes and examine their possible involvement in colon cancer. The expression of these four genes was measured by real time-PCR in 114 patients with colorectal cancer, and tumor characteristics were analyzed in each patient. SNAIL expression was associated with downregulation of CDH1 (P < 0.001) and VDR (P < 0.001) gene products. We also found a positive correlation between CDH1 and VDR expressions. However, the association between SNAIL and CDH1 was not found in patients with high expression of ZEB1. We observed a correlation between downregulation of: a) ZEB1 and presence of polyps in surgical resections; b) VDR and poor differentiation and c) CDH1 and poor differentiation, vascular invasion, presence of lymph node metastases and advanced stages; as well as a trend toward a correlation between SNAIL expression in tumors and vascular invasion. The correlations between SNAIL, CDH1, VDR and ZEB1 and the association between reduced expression of CDH1 and VDR and aggressive tumor characteristics emphasize the value of analyzing these genes in colon cancer patients for prognostic purposes and for predicting response to possible therapies with vitamin D or its analogs.
Peña
Cristina
C
Department of Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain.
García
José Miguel
JM
Silva
Javier
J
García
Vanesa
V
Rodríguez
Rufo
R
Alonso
Isabel
I
Millán
Isabel
I
Salas
Clara
C
de Herreros
Antonio García
AG
Muñoz
Alberto
A
Bonilla
Félix
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009367:Neoplasm Staging; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000706:statistics & numerical data; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000071799:Zinc Finger E-box-Binding Homeobox 1
D015820:Cadherins; D018398:Homeodomain Proteins; D018167:Receptors, Calcitriol; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1