Staff Biography
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Heather E. Kleiner, PhD.
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ContactPhone: (318) 675-8559 Team MembershipCancer Prevention and Control Group--Chemoprevention Translation Research: Breast Cancer Focus Group & Experimental Therapeutics Group Cancer Cell Biology: Cellular Motility and Invasion Group Toxicology Research Interest Group |
Education / Research / Publications
Education / Professional Experience
Research Interest
We are investigating specific natural products for their ability to block breast and skin carcinogenesis using both animal and cell-based models. We are interested first in how chemicals cause cancer, how carcinogens are metabolized, and how to block carcinogen activation. Humans are exposed to low levels of carcinogens throughout their lifetime. We believe that the use of natural products, to which humans are exposed in the diet, can be beneficial in the prevention of many types of cancer. Another area we plan to explore is how continuous exposure to carcinogens might cause premalignant or malignant cells to become more aggressive. We are currently investigating the mechanisms of action of citrus auraptene, and 1’-acetoxychavicol acetate, and have found that they block invasion, proliferation in breast cancer cells in culture.
Project 1: Breast Cancer Chemoprevention
Recently we showed that dietary exposure to citrus auraptene blocked N-methylnitrosourea induced mammary carcinogenesis in rats. In another study we have evidence that auraptene induces carcinogen-detoxifying enzymes such as glutathione S-transferase, in a manner that is dependent upon Nrf-2 and the antioxidant response element. We have identified auraptene in the serum, liver, and mammary glands of rats indicating that it is bioavailable. We also investigated auraptene and a ginger compound, 1’-acetoxychavicol acetate in human breast cancer MDA-MB-231 cells in culture. Both compounds blocked invasion, cell proliferation, and viability. 1’-acetoxychavicol acetate also activated the pro-apoptotic protein caspase-3 in MDA-MB-231 cells even at 6 h of treatment. Future studies are designed to understand more about the pharmacokinetics of auraptene, to determine the role of its effects on Nrf-2 and the antioxidant response element in its chemopreventive effects, and to further delineate its mechanism of action in the rat mammary model.
Project 2: Skin Cancer Chemoprevention
In collaboration with Dr. John Clifford (Biochemistry) we have investigated 1’-acetoxychavicol acetate, a crude ginger extract, and fluocinolone acetonide in transgenic mice that constitutively express signal transducer and activator of transcription 3 (Stat3). These mice, which are exquisitely sensitive to Squamous cell carcinomas, were obtained from Dr. John DiGiovanni (UTMD Anderson Cancer Center). Preliminary results suggested that both 1’-acetoxychavicol acetate and fluocinolone acetonide decreased tumor development in the mice. Additionally, the ginger extract and fluocinolone acetonide blocked tumor promoter induced hyperproliferation of skin.
Project 3: Development of models to test oncolytic virotherapy
In collaboration with Dr. J. Mike Mathis (Cellular Biology and Anatomy) we have initiated three hamster carcinogenesis models to be used for oncolytic virotherapy. These models include (1) N-methylnitrosourea induced breast cancer, (2) diethylstilbestrol/7,12-dimethylbenz[a]anthracene induced breast cancer/stomach cancer/melanoma, and (3) a pancreatic cancer model. We have successfully propagated a breast cancer cell line from the first study. We have also harvested numerous tumors from the second study, including melanomas,Squamous cell carcinomas of the skin, and tumors of the stomach, breast, ovaries, uterus, spleen, liver, and ascites fluid. These cell lines will then be used to test replicative ability of the oncolytic viruses.
Specialized Techniques/Procedures
- Cell culture, Cell proliferation assay, cytotoxicity assay, in vitro invasion assay (Matrigel).
- Immunohistochemistry.
- Western blotting.
- PCR, breeding, and genotyping of mouse colonies
- Cytochrome P450 assays
- Glutathione S-transferase assays
- HPLC-UV, fluorescence detection
- Chemical-induced animal models of cancer: skin (melanoma and non-melanoma), breast, stomach, pancreas. [mice, rats, hamsters]
- 32P-postlabeling, detection of DNA adducts
Selected Publications