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Title: The candidate tumor suppressor CST6 alters the gene expression profile of human breast carcinoma cells: Down-regulation of the potent mitogenic, motogenic, and angiogenic factor autotaxin

Journal Article · · Biochemical and Biophysical Research Communications
 [1];  [2];  [3];  [4];  [5];  [1];  [3];  [6]
  1. Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (United States)
  2. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore (United States)
  3. Research Core Facility, Louisiana State University Health Sciences Center, Shreveport (United States)
  4. Department of Pharmacology, Wayne State University School of Medicine, Detroit (United States)
  5. Laboratory of Pathology, National Cancer Institute, NIH, Bethesda (United States)
  6. Department of Cellular Biology and Anatomy, Louisiana State University Health Sciences Center, Shreveport (United States) and Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport (United States)

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 First evidence that CST6 plays a role in the modulation of genes, particularly, genes that are highly relevant to breast cancer progression.

OSTI ID:
20798780
Journal Information:
Biochemical and Biophysical Research Communications, Vol. 340, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2005.11.171; PII: S0006-291X(05)02703-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
Country of Publication:
United States
Language:
English

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