SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue.
SNAI1, ZEB1, E-cadherin (CDH1), and vitamin D receptor (VDR) genes regulate the epithelial-mesenchymal transition (EMT) that initiates the invasion process of many tumor cells. We hypothesized that this process could also affect the behavior of normal cells adjacent to the tumor. To verify this hypothesis, the expression level of these genes was determined by quantitative RT-PCR in tumor, normal adjacent, and normal distant tissues from 32 colorectal cancer (CC) patients. In addition, we extended the study to human HaCaT normal keratinocytes and SW480-ADH colon cancer cells co-cultured with SW480-ADH cells overexpressing the mouse Snai1 gene. Of 18 CC cases with SNAI1 expression in tumor tissue, five also had SNAI1 in normal adjacent tissue (NAT). Expression of SNAI1 in tumor tissue correlated with downregulation of CDH1 and VDR genes in both tumor (P=0.047 and P=0.014, respectively) and NAT lacking SNAI1 expression (P=0.054 and P=0.003). ZEB1 expression was directly related to VDR expression in tumor tissue (r=0.39; P=0.027) and inversely to CDH1 in NAT (r=-0.46; P=0.010). CDH1 and VDR were also downregulated in SW480-ADH and MaCaT cells, respectively, when they were co-cultured with Snai1-expressing cells. Furthermore, cytokine analysis showed differences in the conditioned media obtained from the two cell types. These results indicate that histologically normal tissue adjacent to tumor tissue expressing the EMT-inducing gene SNAI1 shows alterations in the expression of epithelial differentiation genes such as CDH1 and VDR.
Peña
C
C
Department of Medical Oncology, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain.
García
J M
JM
Larriba
M J
MJ
Barderas
R
R
Gómez
I
I
Herrera
M
M
García
V
V
Silva
J
J
Domínguez
G
G
Rodríguez
R
R
Cuevas
J
J
de Herreros
A G
AG
Casal
J I
JI
Muñoz
A
A
Bonilla
F
F
D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D011905:Genes, ras / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D000071799:Zinc Finger E-box-Binding Homeobox 1
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D018398:Homeodomain Proteins; D018167:Receptors, Calcitriol; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1