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Dr. Mong-Hong Lee

Dr. Mong-Hong Lee

Regular Member

The University of Texas MD Anderson Cancer Center
Department of Molecular and Cellular Oncology

Cell cycle is a series of biochemical events that are controlled by both positive regulators and negative regulators. Cyclin dependent kinases (Cdks) and their Cyclin partners are the positive regulators while the Cyclin-dependent kinase inhibitors (CKIs) are important negative regulators. Our research goals are to characterize the regulatory mechanism of cell cycle proliferation and identify the roles of CKIs in cell cycle regulations and cancer formation.

We have investigated whether there is a link between HER-2/neu oncogenic signals and p27 Kip1, a CKI, regulation in breast cancer by assessing the immunocytochemical staining pattern of p27 in the normal and neoplastic breast tissues. We showed that immunohistochemical screening of breast cancer samples revealed that downregulation of p27 correlated with HER-2/neu overexpression for promoting breast cancer formation. To address the molecular mechanism of this inverse correlation, we found that reduction of p27 is caused by enhanced ubiquitin-mediated degradation, and the HER-2/Grb2/MAPK pathway is involved in the decrease of p27 stability. Also, HER-2/neu activity causes mislocation of p27 and JAB1, an exporter of p27 and subunit of COP9 signalosome, into the cytoplasm, thereby facilitating p27 degradation. These results reveal that HER-2/neu signals reduce p27 stability and thus present potential points for therapeutic intervention in HER-2/neu associated cancers.

In addition, we have identified 14-3-3 sigma as a new class of CKI. 14-3-3 sigma, implicated in cell cycle arrest by p53, was cloned by expression cloning through Cdk2 association. We found that overexpression of 14-3-3 sigma obstructs cell cycle entry by inhibiting cyclin-Cdk activity and enhancing p53 tumor suppressive activity. More recently, we showed that 14-3-3 sigma inhibits Akt activity and blocks Akt-mediated acceleration of p27 Kip1 turnover rate. In addition, 14-3-3 sigma inhibits Akt-mediated p27 Kip1 phosphorylation that targets p27 Kip1 for nuclear export and degradation. 14-3-3 sigma inhibits cell survival and tumorigenicity of Akt-activating breast cancer cell. Significantly, low expression of 14-3-3 sigma in human primary breast cancers correlates with overexpression of HER2 and cytoplasmic location of p27 Kip1. These findings define 14-3-3 sigma as a negative regulator of the cell cycle progression and suggest that it has an important function in preventing breast tumor cell growth.

A tutorial in this lab would offer research experience in both cell biology and molecular biology. Aspects of cell cycle regulation and their involvement in cancer formation will be emphasized. Molecular biology and cell biology techniques will be taught and introduced, including PCR, expression cloning, differential display, FACS, fluorescence microscopy, gene knock out and in situ hybridization.



MDACC Faculty

Program Affiliations:

Program in Cancer Biology

Program in Genes and Development

Contact Information

Phone: 713.794.1323


Office: MDA Y7.6075 (Unit 79)

Title: Professor


Ph.D. - University of Pittsburgh - 1993