Dept. of Biological Sciences

Hexin Chen

Assistant Professor of Biological Sciences
Ph.D., 2000, University of Nebraska-Lincoln

Office: CLS 301
803-777-2928
hchen@biol.sc.edu


"Thank you Turner BioSystems for granting us a Modulus Single Tube Luminometer"

Role of HOX genes in mammary gland development and breast cancer.

It is widely accepted that many of the molecular pathways that underlie carcinogenesis represent aberrations of the normal processes that control embryogenesis. HOX genes encode a large family of transcriptional regulatory proteins which control body planning during embryonic development. Null mutation of HOX genes in animal models result in different extents of developmental defects ranging from altered tissue architecture to neonatal death. In recent years, HOX genes are found to be misexpressed in a variety of cancers. But their exact molecular functions in tumorigenesis remain largely unknown. The research goal in my laboratory is to elucidate the functions and mechanisms of action of HOX genes in mammary gland development and breast tumorigenesis.

Current Research Projects:

Project I. Role of HOXB7 in breast tumorigenesis.
Our recent data suggested that Hoxb7 plays dual roles in oncogene Her2/neu-induced tumorigenesis: inhibition of tumor initiation and promotion of tumor growth and metastasis. Taking advantage of our transgenic animal model, we are investigating the dual role of Hoxb7 in Her2-induced tumorigenesis at three levels: 1) At the tissue level, we are addressing whether overexpression of Hoxb7 causes microenviromental changes, which in turns regulates tumor formation and progression; 2) At the cellular level, we are studying the role of Hoxb7 in cellular proliferation, differentiation and apoptosis in both normal epithelial and tumor cells; 3) At the molecular level, we are dissecting both Hoxb7 and Her2/neu signaling pathways using both genomic, proteomic and biochemical approaches.

Project II. HOXA5-indcued apoptosis in breast cancer cells
Overexpression of HOXA5 in breast cancer cells can cause apoptosis in a p53-independent but caspase 2 and 8-dependent pathways. It still remains unknown what conveys the apoptotic signals from HOXA5 to the caspase cascade. As a transcriptional factor, HOXA5 may exert its functions through regulating the expression of a variety of target genes. Our current efforts are focused on functionally analyzing the HOXA5 target genes identified by microarray analysis.

Project III. HOX regulation of normal and breast cancer stem cells
HOX genes are well-known for their roles in regulating self-renewal and differentiation of hematopoeitic stem cells. Recently, much more progresses have been made in isolation and characterization of normal and breast tumor stem cells. Gain- and loss- of function studies have shown that HOX genes play an important role in mammary gland development and breast tumorigenesis. It will be of great interest to investigate whether/how HOX genes get involved in regulating self-renewal and/or differentiation of mammary and breast cancer stem cells.


Selected Publications:

Chen H, Ji Shin Lee, Xiaohui Liang, Huiping Zhang, Tao Zhu, Zhe Zhang, M. Evangeline Taylor, Cynthia Zahnow, Lionel Feigenbaum, Alan Rein, and Saraswati Sukumar1 (2008). Hoxb7 inhibits transgenic HER2/neu-induced mouse mammary tumor onset but promotes progression and lung metastasis. Cancer Res. 68:3637-44.

Wu X, Chen H, Rubin E, Parker B, Lee J, Argani P, and Sukumar S. (2006). HOXB7, a homeodomain protein, is overexpressed in breast cancer and confers epithelial mesenchymal transition. Cancer Res. 66:9527-34.

Rubin E, Wu X, Zhu T, Cheung C, Chen H, Lorincz A, Pandita R, Sharma G, Ha M, Gasson J, Hanakahi L, Pandita T, and Sukumar S. (2006). A role for the HOXB7 homeodomain protein in DNA repair. Cancer Res. 67:1527-35.

Chen H, Zhang H, Xinyan Wu and Sukumar S. (2007). HOXA5 acts directly downstream of RARβ and contributes retinoic acid-induced apoptosis in breast cancer cells. Cancer Res. 67:8007-13.

Chen H, Rubin E, Zhang H, Garrett E, Jie C, Chung S, Biswal S, and Sukumar S. (2005). Identification of transcriptional targets of HOXA5. J. Bio. Chem. 280:19373-80.

Chen H, Chung S and Sukumar S. (2004). HOXA5-induced apoptosis in Hs578T cells is mediated by caspase-2 and caspase-8. Mol. Cell. Biol. 24:924-935.

Chen H., and Sukumar S. (2003). HOX genes: emerging stars in cancer. Cancer Biol. and Ther. 2:524-5.

Chen H, and Sukumar S. (2003). The role of homeobox genes in mammary gland development and breast cancer (review). J. Mammary Gland Biol. Neoplasia 8:159-75.


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