Journal Article

Deregulated expression of the <i>PER1</i>, <i>PER2</i> and <i>PER3</i> genes in breast cancers

Shou-Tung Chen, Kong-Bung Choo, Ming-Feng Hou, Kun-Tu Yeh, Shou-Jen Kuo and Jan-Gowth Chang

in Carcinogenesis

Volume 26, issue 7, pages 1241-1246
Published in print July 2005 | ISSN: 0143-3334
Published online March 2005 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgi075
Deregulated expression of the PER1, PER2 and PER3 genes in breast cancers

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Disruption of circadian rhythm may be a risk factor in the development of breast cancer, but molecular changes in circadian rhythm controlled genes in breast cancer cells are still unexplored. We used immunohistochemical staining, methylation specific PCR and direct sequencing methods to analyze molecular changes in three most important genes, namely PER1, PER2 and PER3, in circadian rhythm in 55 cases of breast cancer of Taiwanese women. Our results reveal disturbances in the expression of the three period (PER) genes in most (>95%) of the breast cancerous cells in comparison with the nearby non-cancerous cells. The PER gene deregulation is not caused by genetic mutations but most probably by methylation of the PER1 or PER2 promoter. Methylation of the PER gene promoters has a strong correlation with c-erbB2 expression (P = 0.017). Since the circadian clock controls expression of cell-cycle related genes, we suggest that disturbances in PER gene expression may result in disruption of the control of the normal circadian clock, thus benefiting the survival of cancer cells and promoting carcinogenesis. Differential expression of circadian genes in non-cancerous and cancerous cells may provide a molecular basis for chronotherapy of breast cancer.

Keywords: PBS, phosphate buffered saline; PER, period genes; Period 1, PER1; Period 2, PER2; Period 3, PER3; SCN, suprachiasmatic nucleus

Journal Article.  4636 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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