Altered oncogene, tumor suppressor and cell-cycle gene expression in PANC-1 cells cultured with the pleiotrophic 5-lipoxygenase inhibitor, MK886, assessed with a gene chip

We describe a genomic response of mRNAs associated with a subset of oncogen es, tumor suppressor and cell cycle-related genes in proliferating human Pa nc-1 pancreatic cancer cells after 24 hours of culture with MK886, a pleotr ophic 5-lipoxygenase inhibitor. Ninety-eight of these cDNAs are represented in one of the sub-arrays included in the Clontech Human cDNA Expression Ar ray. In this initial analysis, control cells exhibited apparent widespread low levels of disparate mRNA synthesis. In cells cultured with 40 mu M MK88 6 for 24 hr; while most expressed genes, including a number of specific pro liferation-enhancing genes such as c-myc were inhibited 19 other ones inclu ding some countervailing genes including tyrosine SRC protein kinase, cycli ns B1 and D1, CDC25B phosphatase and 40s ribosomal S19, amounting to 19 pel cent of the cDNAs resident on the chip were up-regulated at > 1.10 experim ental/control values., Therapy-induced activation of compensatory prolifera tive genomic responses provides an additional explanation why malignant cel ls can fail therapy. Among their many tuture uses, gene chips clearly will be an extremely powerful tool for identifying relationships between the hie rarchical lineal and non-lineal control and implementation-related cellular events and for identitying potential molecular targets tor cancel. therapy .