Research Interests
Hormones and Cancer: Breast
Our main interest is the study of hormones and their involvement in the causation of many of the most prevalent cancers. Particular emphasis is placed on studying the role of hormones, and other growth regulators in the initiation, promotion, and progression of hormonal cancers, mainly breast, but also prostate, ovarian, and endometrium. Little is known about the complex cellular and molecular events leading to the induction of these hormonally-related neoplasms in either animals or humans.
Hormonal induction of neoplasia characteristically involves tissue and species specificity, sustained and prolonged hormonal exposure, and long induction or latency periods. Mechanisms of hormonal oncogenesis involve enhanced cell proliferation and altered differentiation, protooncogene and suppressor gene expression; mitotic kinase over-expression, chromosomal instability and aneuploidy.
Our approach to elucidating mechanisms of hormonally-related cancer causation, particularly estrogens, is multi-disciplinary and includes: 1. molecular endocrinology: steroid-receptor interactions, hormonal regulation of DNA, RNA, and protein synthesis. 2. regulation of gene and protein expression, RNA synthesis and isolation, enzyme and protein synthesis, chromatin and chromosomal protein regulation. 3. cell and molecular biology: cell cycle (cyclins, cdks, inhibitors of p27, p21, p16) deregulation and cell proliferation; primary epithelial and tumor cell growth; growth factors; protooncogene expression (c-myc, c-jun, c-fos), gene amplification; suppressor gene expression (p53, WT1); genomic instability, molecular cytogenetics, CGH, and FISH.
The estrogen-induced ectopic uterine tumor in kidneys of the Syrian hamster and the estrogen-induced mammary tumor of the female ACI rat are the primary animal models used in these studies.
Liao, D.J., X. Hou, S. Bai, S.A. Li, and J.J. Li. An Unusual Deregulation of Cell Cycle Components in Early and Frank Estrogen-induced Renal Neoplasias in the Syrian Hamster. Carcinogenesis, 21:2167-2173, 2000.
Li, J.J., D. Papa, M.F. Davis, S.J. Weroha, M. Aldaz, K. El-Bayoumy, J. Ballenger, O. Tawfik, S.A. Li. Ploidy Differences Between Hormone- and Chemical Carcinogen-induced Mammary Neoplasms: Relation to Human Breast Cancer. Molec. Carcinogen., 33:56-65, 2002.
Li, S.A., S.J. Weroha, O. Tawfik, and J.J. Li. Prevention of Solely Estrogen-induced Mammary Tumors by Tamoxifen: Evidence for Estrogen Receptor Mediation. J. Endocrinol., 175:297-305, 2002.
Papa D, Li SA, Li JJ (2003) Comparative Genomic Hybridization of Solely Estrogen-induced Ectopic Uterine-like Stem Cell Neoplasms in the Hamster Kidney: Nonrandom Chromosomal Alterations. Mol Carcinogen 38:97-105.
Li JJ, Li SA (2003) Causation and Prevention of Solely Estrogen-induced Oncogenesis: Similarities to Human Ductal Breast Cancer. Adv Exp Med Biol 532:195-207.
Li JJ, Salisbury J, Li SA (2004) Chromosomal Instability: A New Paradigm for Estrogen-induced Oncogenesis. In: Hormonal Carcinogenesis IV (Eds. Li JJ, Llombart-Bosch A, Li SA), Springer-Verlag, New York, p. 19-33.
Li JJ, Weroha SJ, Lingle WL, Papa D, Salisbury JL, Li SA (2004) Estrogen Mediates Aurora-A Overexpression, Centrosome Amplification, Chromosomal Instability and Breast Cancer in Female ACI Rats. Proc Natl Acad Sci USA 101:18123-18128.
Weroha, S.J., S.A. Li, J.J. Li. (2006). Overexpression of Cyclin D1 and D3 During Extrogen-induced Mammary Gland Oncogenesis in Female ACI Rats. Carcinogenesis, 27:491-498.
Hontz AB, Li SA, Lingle WL, Negron V, Bruzek A, Salisbury JL, and Li JJ (2007) Aurora A/B Overexpression and Amplified Centrosomes in Early Estrogen-induced Tumor Foci in the Syrian Hamster Kidney: Implications for Chromosomal Instability, Aneuploidy, and Neoplasia. Cancer Res. 67:2957-2963.
Jonathan J. Li, Ph.D.
Professor
Department of Pharmacology, Toxicology and Therapeutics
The University of Kansas Medical Center
MS1018,
3901 Rainbow Boulevard
Kansas City, KS 66160
Phone: (913) 588-4760
Fax: (913) 588-4740
E-mail: jli1@kumc.edu
Curriculum Vitae in PDF Format
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The University of Kansas Medical Center