Dysregulated expression of HOX and ParaHOX genes in human esophageal squamous cell carcinoma.
Homeobox genes function as master regulators in embryonic morphogenesis. We hypothesized that homeobox genes are essential to maintain tissue- or organ-specificity even in adult body and that the dysregulated expression of homeobox genes results in tumor development and progression. To better understand the roles of homeobox genes in development and progression of esophageal cancer, we analyzed the expression patterns of 39 HOX genes and 4 ParaHOX (CDX1, CDX2, CDX4 and PDX1) genes in esophageal squamous cell carcinoma (ESCC) and normal esophageal mucosa tissues. A total of 48 primary ESCC tissues and 7 normal esophageal mucosa tissues were resected from patients who underwent radical surgery without any preoperative chemotherapy or radiotherapy. The expression of HOX and ParaHOX genes were analyzed by a quantitative real-time RT-PCR method and immunohistochemistry. The expression levels of 24 HOX genes, CDX1, CDX2 and PDX1 were significantly higher in ESCC compared to normal mucosa (p<0.01, Mann-Whitney U test). The Immunohistochemical study revealed that HOXA5 and D9 proteins were more cytoplasmic in ESCC than normal mucosa cells. Our data indicate that the disordered expression of HOX and ParaHOX genes are involved in the development of ESCC or its malignancy.
Takahashi
Osamu
O
Division of Cancer-Related Genes, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
Hamada
Jun-Ichi
J
Abe
Motoki
M
Hata
Shinya
S
Asano
Toshimichi
T
Takahashi
Yoko
Y
Tada
Mitsuhiro
M
Miyamoto
Masaki
M
Kondo
Satoshi
S
Moriuchi
Tetsuya
T
D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
D018398:Homeodomain Proteins; D012333:RNA, Messenger