Applications of DNA Microarray Technology in Cancer Research - DNA Microarray Technology and Data Analysis in Cancer Research - page 19

• Expression of a gene is not changed by BCR-ABL as compared to the

control, and imatinib treatment increases the expression level of the
gene (Pattern H).

• Expression of a gene is not changed by BCR-ABL as compared to the

control, and the expression level of the gene remains the same upon
imatinib treatment (Pattern I).

Detailed explanations for these patterns are described in Table 2.1. In
summary, these patterns have changed our way of interpreting DNA
microarray data. What we learned from this study is that, in oncogene-
stimulated cell proliferation, an upregulated gene is not always positively
involved in cancer development, a downregulated gene is not always
negatively involved in cancer development, and, importantly, a gene with
no change in expression may also be critically involved in cancer develop-
ment. Thus, the expression level of a gene is relative and does not always
reflect its function. It could be misleading to determine the function of
a gene based on the expression level of the gene.

2.3.2. Cell line study

The abovementioned explanations of our microarray data are largely
different from those most people would have. We tested these ideas by
performing an independent microarray experiment in a totally different
assay system. We studied gene expression profiling in BCR-ABL-
expressing lymphoid cells before and after treatment with imatinib. We
first made a B-lymphoid cell line whose growth does not depend on BCR-
ABL, and the control cell line is the parental line that does not express
BCR-ABL (Hu et al ., 2004). Our results also show the gene expression
patterns A-J described above, allowing us to reach the same conclusions
that an upregulation, downregulation, or no change of expression of a gene
does not necessarily reflect the role of this gene in tumor cell growth.
A clear conclusion can be drawn by having a critical control that repre-
sents a situation when the function of the oncogene of interest is inhibited
genetically or by an inhibitory agent.