N-cadherin is regulated by activin A and associated with tumor aggressiveness in esophageal carcinoma.
OBJECTIVE
Activin A is a member of the transforming growth factor beta superfamily and plays an important role in the differentiation of embryonic stem cells. We have reported previously that the expression of activin A is associated with lymph node metastasis in esophageal cancer, and our purpose in the current work is to clarify the molecular mechanism of the aggressive behavior of tumors that have high activin A expression.


METHODS
We have compared the gene expression profiles of human esophageal carcinoma cell lines that were stably transfected with activin beta A, which is a subunit of activin A, with those of control human esophageal carcinoma cell lines, using a cDNA microarray.


RESULTS
We found that the expression level of neuronal cadherin (N-cadherin) was higher in the transfectants than in the control cells. N-cadherin was located on the cell surface of the transfectants, irrespective of the expression of epithelial cadherin (E-cadherin), and the expression of N-cadherin mRNA was significantly associated with that of activin beta A mRNA in clinical samples of esophageal carcinoma (n = 51; r = 0.855). A clinicopathologic analysis suggested that expression of N-cadherin mRNA was associated with the depth of tumor wall invasion, and a group of patients with high expression of N-cadherin mRNA showed a significantly poorer prognosis than a group of patients with low N-cadherin expression (P = 0.046).


CONCLUSIONS
These results indicate that activin A might mediate the expression of N-cadherin and that this may be associated with depth of invasion and poor prognosis.
Yoshinaga
Keiji
K
Department of Molecular and Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Inoue
Hiroshi
H
Utsunomiya
Tohru
T
Sonoda
Hideto
H
Masuda
Takaaki
T
Mimori
Koshi
K
Tanaka
Yoichi
Y
Mori
Masaki
M
D028341:Activins / Q000502:physiology*; D000368:Aged; D015820:Cadherins / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D028322:Inhibin-beta Subunits / Q000502:physiology*; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D014162:Transfection; D014407:Tumor Cells, Cultured
D015820:Cadherins; D012333:RNA, Messenger; C422405:activin A; D028341:Activins; D028322:Inhibin-beta Subunits