Thea D. Tlsty
Department of Pathology, University of California at San Francisco, San Franctsco, California 94143-0506, USA
(Tel: 415-502-6115 Fax: 415-502-6163 E-mail: ttlsty@itsa.ucsf.edu)
Senescence and tight control of genomic stability are believed to be important barriers to the development of malignant lesions. We show that, in contrast to human fibroblasts, senescence is not an insurmountable barrier to further growth in isogenic human mammary epithelial cells (HMECS). HMECs overcome the senescence barrier at a high frequency and proliferate for an extended period of time with eroding telomeric sequences. These cells subsequently enter telomere-based crisis and generate the types of chromosomal abnormalities seen in the earliest lesions of breast cancer. Growth past senescent barriers may be a pivotal event in the earliest steps of carcinogenesis providing multiple, fundamental genetic changes predicating oncogenic evolution. These differences between epithelial cells and fibroblasts provide new insights into the mechanistic basis of neoplastic transformation.
Thea D. Tlsty 1973 B.S. University of South Florida, Tampa, FL
1980 Ph.D. Washington University, St. Louis, MO
1978-1980 Predoctoral Fellow Washington University, St. Louis, MO
1981-1984 Postdoctoral Fellow Stanford University, Stanford, CA
1984-1985 Senior Research Associate Stanford University, Stanford, CA
1985-1992 Assistant Professor of Pathology and Member, UNC Lineberger Comprehensive Cancer Center, Curriculum in Genetics; Curriculum in Toxicology: Program In Molecular Biology & Biotechnology, University of North Caroline at Chapel Hill, NC
1992-1995 Associate Professor of Pathology and Member, Lineberger Comprehensive Cancer Center, University of North Caroline at Chapel Hill, NC
1995-1996 Associate Professor of Pathology, Director of Molecular Pathology, Member: Cancer Research Institute; Program in Biological Science; Program in Biomedical Sciences, University of California at San Francisco, CA
1996-present Professor of Pathology, Director of Molecular Pathology, Member: Cancer Research Institute: Program in Biological Science; Program in Biomedical Sciences, University of California at San Francisco, CA