Daniel Medina, Ph.D.
Department of Molecular and Cellular Biology
Ph.D.: University of California, Berkeley
Cellular and Molecular Events Critical for Premalignant Progression
Breast cancer is the major cancer of women in the United States and will cause over 40,000 deaths in 2007. Although the main risk factors are genetics, age and reproductive history, fully 60 percent of human breast cancers are not defined by these risk factors. Thurs, the etiology and underlying mechanisms of breast cancer remain elusive.
Rodent models for breast cancer have been important for elucidating the histopathology, tumor progression, etiological agents, and molecular mechanisms involved in this disease. We are using traditional mouse and rat breast cancer models to investigate fundamental questions regarding the molecular changes involved in tumor development, as well as in hormone-mediated prevention of the disease. In addition, we are developing new cell lines of human ductal carcinoma in situ to investigate the molecular alterations critical for progression from the non-invasive to the invasive phenotype. The ability of these cell lines to grow as xenografts in immunocompromised mice has recently been attained using a novel transplantation method. In the mouse model, we have developed an in vivo-in vitro model where the sequential development of the malignant phenotype is represented in different defined cell populations. These populations are being examined by molecular biological approaches to detect, characterize and define the functional properties of genes uniquely up-regulated or down-regulated at each stage of neoplastic development. Global gene expression methods are being utilized to detect several unique genes up-regulated in the tumorigenic phenotype. The function of TP53, a known tumor suppressor gene, has been examined in a new model where p53 has been deleted from the mammary gland. The role of hormones in genetic instability and tumorigenesis is being examined in this model.
Baylor College of Medicine
One Baylor Plaza, Cullen 135C
Houston, TX 77030
- Loehberg CR, Thompson T, Kastan MB, Edwards DG, Kittrell FS, Medina D, Conneely OM and O'Malley BW. (2007). ATM and p53 are potential mediators of chloroquine-induced resistance to mammary carcinogenesis. Cancer Res (in press).
- Allred DC, Wu Y, Mao S, Nagtegael ID, Lee S, Perou CM, Mohsin SK, O'Connell P, Tsimelzon A and Medina D. (2007). Ductal carcinoma in situ and the emergence of diversity during breast cancer evolution. Clinical Cancer Res (in press).
- Abba MC, Cai WW, Donehower L.A, Kittrell FS, Medina D and Aldaz CM. (2007). Identification of novel amplification gene targets in mouse and human breast cancers: synteneic cluster mapping to mouse Ch8f1 and human Ch13q34. Cancer Res 67:4101-4117.
- Lee S, Medina D, Tsimelzon A, Mohsin SK, Mao S, Wu Y and Allred DC. (2007). Alteration of genes and pathways in hyperplastic enlarged lobular units, the early precursors of breast cancer. Am J Path 171:1-11.
- Rajkumar L, Kittrell FS, Guzman RC, Brown PH, Nandi S and Medina D. (2007). Hormone-induced protection of mammary tumorigenesis in genetically engineered mouse models. Breast Cancer Res 9:R12 [Epub ahead of print].
- Goepfert TM, Moreno-Smith M, Edwards DG, Pathak S, Medina D and Brinkley WR. (2006). Loss of chromosomal integrity drives rat mammary tumorigenesis. International J Cancer 120:985-994.
- Deugnier MA, Faraldo MM, Teuliere J, Thiery JP, Medina D and Glukhova MA. (2006). Isolation of mouse mammary epithelial progenitor cells with basal characteristics from the Comma-Dβ cell line. Dev Biol 293:414-425.
- Lee S, Mohsin SK, Mao S, Hilsenbeck SG, Medina D and Allred DC. (2006). Hormones, receptors, and growth in hyperplastic enlarged lobular units: early potential precursors of breast cancer. Breast Cancer Res 8:R6, (online).
- Medina D. (2005). Mammary developmental fate and breast cancer risk. Endocrine-Related Cancer 12:1-13.
- Medina D, Kittrell FS, Hill J, Shepard A, Thordarson G and Brown P. (2005). Tamoxifen inhibition of estrogen receptor-α-negative mouse mammary tumorigenesis. Cancer Res 65:3493-3496.