Nucleic Acids Research, Vol 26, Issue 4 1116-1123, Copyright © 1998 by Oxford University Press
WW Kuang, DA Thompson, RV Hoch and RJ Weigel
Differences in gene expression are likely to explain the phenotypic
differences between hormone-responsive and hormone-unresponsive breast
cancer. We have identified differentially expressed cDNAs in the estrogen
receptor (ER)-positive MCF7 breast carcinoma cell line compared with the
ER-negative MDA-MB-231 breast carcinoma cell line. Differential screening
isolated four differentially expressed genes: cytokeratin 8, cytokeratin
18, Hsp27 and GPCR -Br. To identify differentially expressed genes of lower
abundance, suppression subtractive hybridization was utilized and 29
differentially expressed clones were isolated. Sequence analysis revealed
that 11 clones were from previously described genes: HEK8, neuropeptide Y
receptor Y1, p21 WAF-1, p55 PIK, cytokeratin 18 (cloned twice),
fructose-1,6- biphosphatase, cytokeratin 8, TGFbeta1 binding protein,
elongation factor 1alpha2 and pS2. The remaining 18 clones did not match
sequences in the GenBank/EMBL database, indicating that they may be novel
genes. Expression of pS2, neuropeptide Y receptor Y1 and three novel clones
was induced by estradiol, indicating estrogen-responsiveness. The
expression pattern of one novel gene, DEME -6, correlated with expression
of ER and ERF -1/ AP -2gamma in a panel of breast carcinoma cell lines. A
2.6 kb cDNA of DEME -6 was sequenced and contains an open reading frame of
574 amino acids that demonstrates 62.4% similarity with a gene from
Caenorhabditis elegans chromosome III. Expression of DEME -6 was also
detected in primary breast carcinomas but not in normal breast tissue, as
determined by RT-PCR. These findings support the hypothesis that a set of
genes coordinately regulated with ER , but not necessarily
estradiol-responsive, are characteristic of the hormone- responsive breast
cancer phenotype.
ARTICLES
Differential screening and suppression subtractive hybridization identified genes differentially expressed in an estrogen receptor- positive breast carcinoma cell line
Department of Surgery, Stanford University, Stanford, CA 94305, USA.
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