This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Floryk, D. Articles by Huberman, E. Search for Related Content PubMed PubMed Citation Articles by Floryk, D. Articles by Huberman, E.

Differentiation of Androgen-Independent Prostate Cancer PC-3 Cells Is Associated with Increased Nuclear Factor-B Activity

Gene Expression Group, Argonne National Laboratory, Argonne, Illinois

Requests for reprints: Eliezer Huberman, Gene Expression Group, Argonne National Laboratory, Building 202, 9700 South Cass Avenue, Argonne, IL 60439. Phone: 630-252-3820; Fax: 630-252-9155; E-mail: elih{at}anl.gov.com.

Recently, we have reported that inosine 5'-monophosphate dehydrogenase inhibitors, such as mycophenolic acid (MPA), induce the differentiation of PC-3 cells, which are derived from a human androgen-independent prostate cancer, into cells with a phenotype resembling maturing prostate secretory cells. Here, we describe such differentiation induced by the histone deacetylase inhibitor tributyrin. The maturation was defined by cytoplasmic vacuole production and induction of CD10, CD46, CD55, GRP78, keratin 17, and zinc--2-glycoprotein. To identify additional genes associated with tributyrin-induced PC-3 cell differentiation and to gain some insight into the mechanism that underlies this differentiation, we have, by means of microarray analyses, compared tributyrin-induced gene expression patterns with those of MPA, which initiates PC-3 cell differentiation by a dissimilar mode of action. We suggested that genes induced by both tributyrin and MPA would be most likely associated with differentiation rather than with the unique action of each particular inducer. Our results indicated that tributyrin or MPA induced the expression of a large number of common genes, including genes known or assumed to be NF-B dependent. The NF-B dependency of a group of these genes, which included the PC-3 cell differentiation marker keratin 17, was confirmed by using two common NF-B activation inhibitors, Bay11-082 and TMB-8, and p65 subunit of NF-B complex specific small interfering RNA. Taken together, our results implicate both NF-B–dependent and NF-B–independent genes in the processes leading to PC-3 cell differentiation induced by tributyrin and MPA. (Cancer Res 2005; 65(24): 11588-96)

This article has been cited by other articles:

				M. Mimeault, P. P. Mehta, R. Hauke, and S. K. Batra Functions of Normal and Malignant Prostatic Stem/Progenitor Cells in Tissue Regeneration and Cancer Progression and Novel Targeting Therapies Endocr. Rev., April 1, 2008; 29(2): 234 - 252. [Abstract] [Full Text] [PDF]