[Activation of nuclera factor-kappa B and control of the expression of cell adhesion molecules in human prostate cancer cells].
OBJECTIVE
Cell adhesion molecules (CAMs) have been considered to play key roles in cancer metastasis through binding of cancer cells to the endothelial cells or matrix. We have found that constitutive expression of E-selectin, ICAM-1 (intercellular adhesion molecule-1) and VCAM-1 (vascular cell adhesion molecule-1) on the cell surface of prostate cancer cell lines, PC-3 LNCaP, and DU145. In an attempt to explain the highly metastatic potential of these cells, we investigated expression of CAMs. Since these expressed CAMs are known to be regulated by a transcription factor NF kappa B. We have examined if NF kappa B is activated in these prostateccell lines.


METHODS
Expression of E-selectin, ICAM-1. Sialyl-Lewis X, LFA-1 (lymphocyte function-associated antigen-1), integrin alpha 4, and integrin beta 1 were examined by indirect immunofluorescent staining and Western blotting using specific monoclonal antibodies. We then examined whether pro-inflammatory cytokines known to stimulate NF kappa B, IL-1 and TNF, could drive the nuclear translocation of NF kappa B Ten ng/ml of recombinant human IL-1 beta or TNF alpha was added to the cell culture and the CAMs level, as well as nuclear translocation of NF kappa B, was examined.


RESULTS
The staining levels of ICAM-1, VCAM-1, and integrin beta 1 were highly elevated in PC-3 and DU145. In surprising, NF kappa B was retained in the cytoplasm (as an inactive form) and not detectable in the nucleus (active form) as demonstrated by immunofluorescence. Although time-dependent expression of these molecules were explored, the level of ICAM-1 and VCAM-1 on the cell surface were unchanged. However, nuclear translocation of NF kappa B could be induced.


CONCLUSIONS
These observations indicate that while the signaling pathway to NF kappa B is intact, it is not directed to induction of its target CAM genes. It is possible that other transcription factors might be involved in these cells and that they might to be constitutively stimulated during the carcinogenesis of prostate cancer.
Tozawa
K
K
Department of Urology, Nagoya City University School of Medicine.
D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D019040:E-Selectin / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009360:Neoplastic Cells, Circulating; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D016169:Lymphocyte Function-Associated Antigen-1; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1