Gene expression profiling after treatment with the histone deacetylase inhibitor trichostatin A reveals altered expression of both pro- and anti-apoptotic genes in pancreatic adenocarcinoma cells.
Gene expression profiling after treatment with the histone deacetylase inhibitor trichostatin A reveals altered expression of both pro- and anti-apoptotic genes in pancreatic adenocarcinoma cells.
(2004)
Gene expression profiling after treatment with the histone deacetylase inhibitor trichostatin A reveals altered expression of both pro- and anti-apoptotic genes in pancreatic adenocarcinoma cells.
The histone deacetylase inhibitor trichostatin A (TSA) has been previously shown to block cellular growth in G2 and induce apoptosis in
human pancreatic cancer cell lines. In order to better understand this phenomenon, we have analyzed the gene expression profiles in PaCa44
cells after treatment with TSA using microarrays containing 22,283 probesets. TSA was found to cause both the induction and repression of a
large number of genes, although the number whose expression was up-regulated was greater than the number of genes that were downregulated.
When a threshold value of 3 was used as a cutoff level, a total of 306 (3.4%) of the detectable genes had altered expression. When
categorized according to cellular function, the differentially expressed genes were found to be involved in a wide variety of cellular processes,
including cell proliferation, signaling, regulation of transcription, and apoptosis. Moreover, Sp1/Sp3 transcription factor binding sites were
significantly more abundant among TSA-induced genes. One prominent feature was the increased ratio between the levels of expression of
pro-apoptotic (BIM) and anti-apoptotic (Bcl-XL and Bcl-W) genes. This result was confirmed in eight additional pancreatic cancer cell lines
after treatment with TSA, suggesting that this event may be a strong determinant for the induction of apoptosis by TSA.
Moore, Ps; Barbi, Stefano; Donadelli, Massimo; Costanzo, Chiara; Bassi, Claudio; Palmieri, Marta; Scarpa, Aldo,
Gene expression profiling after treatment with the histone deacetylase inhibitor trichostatin A reveals altered expression of both pro- and anti-apoptotic genes in pancreatic adenocarcinoma cells.«Biochimica et Biophysica Acta (BBA)»
, vol. 1693
, n. 3
, 2004
, pp. 167-176