Greater transiency in modulation of gene expression is the predominant difference between the actions of bryostatin 1 and phorbol ester in LNCaP and U937 cells [set 1]

Bryostatin 1, like the phorbol ester PMA, activates protein kinase C (PKC) in vitro but paradoxically blocks many phorbol ester responses in vivo. Results with a limited panel of genes suggested that transiency of action was an important mechanism contributing to this differential cellular response. Here, we examined global gene expression in LNCaP and U937 cell lines to probe the extent to which transiency of action captures the difference in response. While different genes showed different patterns of relative response, the overall pattern was reflective of an initial PMA-like response to bryostatin 1 followed by variable transiency of the continued response. This conclusion was further strengthened by detailed time course measurements by qPCR of selected genes. Merle 23, a bryostatin derivative with biological behavior intermediate between that of bryostatin 1 and PMA, was likewise intermediate for transiency of action. Both the LNCaP and U937 cell lines behaved similarly, but the extent of transiency in response to bryostatin 1 was greater in the LNCaP cells. Forty samples were analyzed in the study; Univariate one-way analysis of variance with planned contrasts (Partek® Genomics Suite 6.5) was used to identify significant changes in gene expression due to bryostatin 1, PMA, and merle 23 treatments in LNCaP and U937 cells. The ANOVA p-values were converted to false discovery adjusted q-values with the method of Storey [Storey 2002] implemented in the R package qvalue [R core team 2013, Dabney and Storey]