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Breast cancer represents one in four of all cancers in women, making it the most common cancer in women. Cyclin D1 has been indicated to play an important role in breast cancer progression. The Cyclin D1 gene (CCND1 or PRAD1) is amplified in up to 20% of human breast cancers. Cyclin D1 protein is overexpressed in over 50% of human mammary carcinomas.

Metazoans require adequate O2 to survive. The more cells a tissue contains, the more O2 is consumed. It is not surprising that O2 sensing pathways are active in fast growing tissues and tumors and regulate their growth. EglN Prolyl Hydroxylases have been found to be O2-sensing enzymes.

A recent genetic study from Drosophila provided a link between Cyclin D and EglN. Frei and Edgar showed that Cyclin D/CDK4 requires prolyl hydroxylase Fatiga (Drosophila EglN) to drive cell growth. More recently, we discovered that knockdown of EglN in human cancer cells downregulates Cyclin D1 levels. In addition, EglN knockout mice showed a similar phenotype to Cyclin D1 knockout mice in mammary gland development. EglN knockout MEFs showed resistance to Ras and dominant-negative p53 transformation.

The mechanisms of how EglN regulates Cyclin D1 and whether EglN could be a drug target in breast cancer therapy will be discussed.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA