J Korean Med Sci.  2004 Apr;19(2):275-282. 10.3346/jkms.2004.19.2.275.

Gene Expression Profiling of Breast Cancers with Emphasis of beta-Catenin Regulation

Affiliations
  • 1Department of Pathology, Dong-A University College of Medicine, Busan, Korea. msroh@netian.com
  • 2Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.
  • 3Department of Surgery, Dong-A University College of Medicine, Busan, Korea.
  • 4Department of Urology, Dong-A University College of Medicine, Busan, Korea.
  • 5Department of Pharmacology, Dong-A University College of Medicine, Busan, Korea.

Abstract

To gain molecular understanding of carcinogenesis of breast cancer, gene expression profiles were analyzed using cDNA microarray representing 4,600 cDNAs in 10 breast cancer samples and the adjacent noncancerous breast tissues from the same patients. The alterations in gene expression levels were confirmed by reversetranscription PCR in four randomly selected genes. Genes that were differently expressed in cancer and noncancerous tissues were identified. 106 (of which 55 were known) and 49 (of which 28 were known) genes were up- or down-regulated, respectively, in greater than 60% of the breast cancer samples. In cancer tissues, genes related to cell cycle, transcription, metabolism, cell structure/motility and signal transduction were mostly up-regulated. Furthermore, three cancer tissues showing immunohistochemically aberrant accumulation of beta-catenin in the nucleus and/or cytoplasm revealed down-regulation of Siah and Axin genes and up-regulation of Wnt and c-myc genes. These findings were highly consistent with Wnt signaling pathway associated with beta-catenin regulation previously suggested by others. Our studies, therefore, provide not only a molecular basis to understand biological processes of breast cancer but also useful resources to define the mechanism of beta-catenin expression in tumorigenesis of breast cancer.

Keyword

Oligonucleotide Array Sequence Analysis; Gene Expression; beta-Transducin Repeat; Containing Proteins; Breast Neoplasms

MeSH Terms

Adult
Breast Neoplasms/*genetics/*metabolism/pathology
Cytoskeletal Proteins/*metabolism
Female
*Gene Expression Profiling/standards
Gene Expression Regulation, Neoplastic
Human
Immunohistochemistry
Middle Aged
*Oligonucleotide Array Sequence Analysis/standards
Reproducibility of Results
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Support, Non-U.S. Gov't
Trans-Activators/*metabolism

Figure

  • Fig. 1 The results of semiquantitative RT-PCR for the 4 tested genes in the 10 breast cancer tissues and the noncancerous tissues, consisting with those from the microarrary studies. N, noncancerous tissue; T, tumor tissue; A, U76248 (Siah); B, AF009674 (Axin); C, D79995; D, X06825 (Tropomyosin 2β).

  • Fig. 2 Immunohistochemical stain for β-catenin in breast cancer. (A) Membranous pattern from case 1 (×200). (B) Aberrantly accumulated pattern in the nucleus and cytoplasm from case 5 (×400).


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