Nucleic Acids Research, Vol 27, Issue 20 4008-4017, Copyright © 1999 by Oxford University Press
JJ Oh, DR Grosshans, SG Wong and DJ Slamon
Amplification and resulting overexpression of the HER-2/ neu proto-
oncogene is found in approximately 30% of human breast and 20% of human
ovarian cancers. To better understand the molecular events associated with
overexpression of this gene in human breast cancer cells, differential
hybridization was used to identify genes whose expression levels are
altered in cells overexpressing this receptor. Of 16 000 clones screened
from an overexpression cell cDNA library, a total of 19 non-redundant
clones were isolated including seven whose expression decreases (C clones)
and 12 which increase (H clones) in association with HER-2/ neu
overexpression. Of these, five C clones and 11 H clones have been confirmed
to be differentially expressed by northern blot analysis. This group
includes nine genes of known function, three previously sequenced genes of
relatively uncharacterized function and four novel genes without a match in
GenBank. Examination of the previously characterized genes indicates that
they represent sequences known to be frequently associated with the
malignant phenotype, suggesting that the subtraction cloning strategy used
identified appropriate target genes. In addition, differential expression
of 12 of 16 (75%) cDNAs identified in the breast cancer cell lines are also
seen in HER-2/ neu -overexpressing ovarian cancer cells, indicating that
they represent generic associations with HER-2/ neu overexpression.
Finally, up-regulation of two of the identified cDNAs, one novel and one
identified but as yet uncharacterized gene, was confirmed in human breast
cancer specimens in association with HER-2/ neu overexpression. Further
characterization of these genes may yield insight into the fundamental
biology and pathogenetic effects of HER-2/ neu overexpression in human
breast and ovarian cancer cells.
ARTICLES
Identification of differentially expressed genes associated with HER- 2/neu overexpression in human breast cancer cells
Department of Medicine, Division of Hematology and Oncology, UCLA School of Medicine, Los Angeles, CA 90095-1678, USA.
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