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Korean Journal of Obstetrics & Gynecology 1997;40(10):2269-2278.
Published online January 1, 2001.
Suppression of Steroid Receptor Function by Retinoblastoma Protein in Breast Cancer Cell Line, MCF 7.
Joon Song, Sung Jin Cho, Kyung Il Lee, Sun Haeng Kim, Jae Sung Kang, Kyu Wan Lee, Jin Yong Lee, Pyong Sahm Ku
1Department of Obstetrics and Gynecology, National medical Center, Institute of Life Science, Korea.
2Department of Obstetrics and Gynecology, Medical School Korea University, Korea.
3Department of Obstetrics and Gynecology, Medical School Seoul National University, Seoul, Korea.
Abstract
Cancer results from mutations that disrupt the harmonious checks and balances that regulate normal cellular growth and development. These mutations arise in two classes of interacting genes:those that facilitate cell growth and tumor formation(oncogenes), in which mutation or overexpression is oncogenic, and those that inhibit these processes(tumor supp-ressor genes) whose loss is oncogenic. The human retinoblastoma(Rb) protein, a tumor suppressor, acts as transcription factor or/and cell cycle regulator. Heterogenous expression of the Rb gene product contributes to the genesis of a diverse group of human neoplasma such as breast, prostate, small cell lu- ng, bladder carcinoma and leukemia. Its structural aberrations were observed in 25% of br- east tumor cell lines studied and 7% of the primary tumors, such as homozygous internal deletions and total deletion. These observations suggest that Rb protein is involved in bre- ast cancer development. Here we report that Rb protein represses steroid receptor function and its involvement of cell cycle process in human breast cancer cell line, MCF7 cells. 1. The overexpression of Rb protein repressed the steroid receptor function in breast cancer cell line, MCF 7. 2. When we introduced the mutant type Rb expression vector(deletion of exon 22), such repression was not observed. 3. By introducing E2F expression vector, the action of Rb protein was repressed. 4. Rb protein modulated the binding patterns of proteins to Kil-GRE site. 5. Flow cytometry analysis showed that Rb protein acts on G0/G1 stage of cell cycle process. These findings provide the molecular basis of breast cancer therapy using Rb protein.
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