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 oncogenes, tumor suppressor and cell cycle-related genes in proliferating human Panc-1 pancreatic cancer cells after 24 hours of culture with MK886, a pleotrophic 5-lipoxygenase inhibitor. Ninety-eight of these cDNAs are represented in one of the sub-arrays included in the Clontech Human cDNA Expression Array. In this initial analysis, control cells exhibited apparent widespread low levels of disparate mRNA synthesis. In cells cultured with 40 microM MK886 for 24 hr, while most expressed genes, including a number of specific proliferation-enhancing genes such as c-myc were inhibited, 19 other ones including some countervailing genes including tyrosine SRC protein kinase, cyclins B1 and D1, CDC25B phosphatase and 40s ribosomal S19, amounting to 19 percent of the cDNAs resident on the chip were up-regulated at > 1.10 experimental/control values. Therapy-induced activation of compensatory proliferative genomic responses provides an additional explanation why malignant cells can fail therapy. Among their many future uses, gene chips clearly will be an extremely powerful tool for identifying relationships between the hierarchical linear and non-linear control and implementation-related cellular events and for identifying potential molecular targets tor cancer therapy.
Anderson
K M
KM
Department of Medicine, Rush Medical College, Chicago, IL, USA.
Alrefai
W A
WA
Bonomi
P
P
Dudeja
P
P
Ou
D
D
Anderson
C
C
Harris
J E
JE
D015153:Blotting, Western; D018076:DNA, Complementary / Q000378:metabolism; D016147:Genes, Tumor Suppressor / Q000187:drug effects / Q000235:genetics*; D019254:Genes, bcl-2 / Q000187:drug effects / Q000235:genetics*; D018816:Genes, cdc / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000187:drug effects / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000378:metabolism; D014407:Tumor Cells, Cultured; D002722:Chlorobenzenes
D018076:DNA, Complementary; D007211:Indoles; D016859:Lipoxygenase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D012260:Ribonucleases; C060893:MK-886; D002722:Chlorobenzenes