Gene Therapy Weekly

Researchers at University of Illinois release new data on gene therapy

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"NM23-H1 is a multifunctional protein, which, in addition to limiting metastasis, has DNase and histidine protein kinase activities. We have identified new functions for NM23-H1 in influencing estrogen receptor alpha (ER alpha)-mediated gene expression. Using a battery of molecular and biochemical techniques, we show that NM23-H1 interacts with ER alpha and increases the ER alpha-estrogen response element (ERE) interaction. When NM23-H1 expression is increased in U2 osteosarcoma and MDA-MB-231 breast cancer cells, transcription of a transiently transfected, estrogen-responsive reporter plasmid is decreased. More importantly, when endogenous NM23-H1 expression is knocked down in MCF-7 human breast cancer cells using small interfering RNA, estrogen responsiveness of the progesterone receptor (PR), Bcl-2, cathepsin D, and cyclin D1 genes, but not the pS2 gene, is enhanced. Furthermore, NM23-H1 associates with the region of the PR gene containing the +90 activator protein 1 site, but not with the ERE-containing region of the pS2 gene, indicating that NM23-H1 mediates gene-specific effects by association with endogenous chromatin. Our studies suggest that the capacity of NM23-H1 to limit the expression of estrogen-responsive genes such as cathepsin D and Bcl-2, which are involved in cell migration, apoptosis, and angiogenesis, may help to explain the metastasis-suppressive effects of this protein," wrote C.D. Curtis and colleagues, University of Illinois.

The researchers concluded: "The complementary abilities of ER alpha and NM23-H1 together to influence gene expression, cell migration, and apoptosis could be key factors in helping to determine tumor cell fate."

Curtis and colleagues published their study in Cancer Research (Interaction of the tumor metastasis suppressor nonmetastatic protein 23 homologue h1 and estrogen receptor alpha alters estrogen-responsive gene expression. Cancer Research, 2007;67(21):10600-10607).

For additional information, contact A.M. Nardulli, University of Illinois, Dept. of Molecular & Integrat Physiol, 524 Burril Hall, 407 S Goodwin Avenue, Urbana, IL 61801, USA.

The publisher's contact information for the journal Cancer Research is: American Association Cancer Research, 615 Chestnut St., 17TH Floor, Philadelphia, PA 19106-4404, USA.

Keywords: United States, Urbana, Biochemical, Biotechnology, Breast Cancer, Breast Carcinoma, Cancer Research, DNase, Enzyme Research, Enzymology, Gene Therapy, Kinase, Oncology, Orthopedics, Osteosarcoma, Women's Health, University of Illinois.

This article was prepared by Gene Therapy Weekly editors from staff and other reports. Copyright 2008, Gene Therapy Weekly via NewsRx.com.