TY - JOUR
T1 - The candidate tumor suppressor CST6 alters the gene expression profile of human breast carcinoma cells
T2 - Down-regulation of the potent mitogenic, motogenic, and angiogenic factor autotaxin
AU - Song, Jin
AU - Jie, Chunfa
AU - Polk, Paula
AU - Shridhar, Ravi
AU - Clair, Timothy
AU - Zhang, Jun
AU - Yin, Lijia
AU - Keppler, Daniel
N1 - Funding Information:
This study was in part supported by a Research Grant CA91785 (DK) and by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (TC). JS received a Takeda Scholar-in-Training Award from the American Association for Cancer Research to present part of this work at the Special Conference on Cancer Research: ‘New Directions in Angiogenesis Research,’ Chicago, October 15–19, 2003. RS was partly supported by Research Grant CA36481 (Bonnie F. Sloane, Wayne State University) from the National Cancer Institute. Our sincere thanks go to Drs. Omar Skalli and Athena W. Lin for critical reading of the manuscript.
PY - 2006/2/3
Y1 - 2006/2/3
N2 - We recently coined CST6 as a novel candidate tumor suppressor gene for breast cancer. CST6 indeed is expressed in the normal human breast epithelium, but little or not at all in breast carcinomas and breast cancer cell lines. Moreover, ectopic expression of CST6 in human breast cancer cells suppressed cell proliferation, migration, invasion, and orthotopic tumor growth. To obtain insights into the molecular mechanism by which CST6 exhibits its pleiotropic effects on tumor cells, we compared global gene expression profiles in mock- and CST6-transfected human MDA-MB-435S cells. Out of 12,625 transcript species, 61 showed altered expression. These included genes for extracellular matrix components, cytokines, kinases, and phosphatases, as well as several key transcription factors. TaqMan PCR assays were used to confirm the microarray data for 7 out of 11 genes. One down-regulated gene product, secreted autotaxin/lyso-phospholipase D, was of particular interest because its down-regulation by CST6 could explain most of CST6's effect on the breast cancer cells. This study thus provides the first evidence that CST6 plays a role in the modulation of genes, particularly, genes that are highly relevant to breast cancer progression.
AB - We recently coined CST6 as a novel candidate tumor suppressor gene for breast cancer. CST6 indeed is expressed in the normal human breast epithelium, but little or not at all in breast carcinomas and breast cancer cell lines. Moreover, ectopic expression of CST6 in human breast cancer cells suppressed cell proliferation, migration, invasion, and orthotopic tumor growth. To obtain insights into the molecular mechanism by which CST6 exhibits its pleiotropic effects on tumor cells, we compared global gene expression profiles in mock- and CST6-transfected human MDA-MB-435S cells. Out of 12,625 transcript species, 61 showed altered expression. These included genes for extracellular matrix components, cytokines, kinases, and phosphatases, as well as several key transcription factors. TaqMan PCR assays were used to confirm the microarray data for 7 out of 11 genes. One down-regulated gene product, secreted autotaxin/lyso-phospholipase D, was of particular interest because its down-regulation by CST6 could explain most of CST6's effect on the breast cancer cells. This study thus provides the first evidence that CST6 plays a role in the modulation of genes, particularly, genes that are highly relevant to breast cancer progression.
KW - Breast cancer
KW - Cytokines
KW - DNA microarrays
KW - Functional genomics
KW - Signaling
KW - Tumor suppressors
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U2 - 10.1016/j.bbrc.2005.11.171
DO - 10.1016/j.bbrc.2005.11.171
M3 - Article
C2 - 16356477
AN - SCOPUS:29244477512
SN - 0006-291X
VL - 340
SP - 175
EP - 182
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -