Mina Bissell, Ph.D., is distinguished scientist at the Lawrence Berkeley National Laboratory. Dr. Bissell has authored more than 300 publications, is a member of five international scientific boards, and is on the editorial board of a dozen scientific journals. Her awards include the Lawrence Award and medal, the Mellon Award from the University of Pittsburgh, the Eli Lilly/Clowes Award from AACR, the first "Innovator Award" of the U.S. Department of Defense for breast cancer research, the Brinker Award from the Susan G. Komen Foundation, the Discovery Health Channel Medical Honor and medal, the H. Lee Moffitt Cancer Center Ted Couch Lectureship and Award, the Pezcoller Foundation-AACR International Award for Cancer Research, the 2008 Excellence in Science Award from the Federation of American Societies for Experimental Biology, and the 2008 American Cancer Society Medal of Honor for Basic Research. In addition, in 2008 she was the first recipient of the Mina J. Bissell Award from the University of Porto in Portugal. Dr. Bissell is a fellow of the AAAS, the American Academy of Arts and Sciences, the Institute of Medicine of the National Academies, and the American Philosophical Society. She has received honorary doctorates from Pierre and Marie Curie University in Paris and from the University of Copenhagen.
A summary of the May 2009 article from Dr. Bissell in Cancer Research is available below:
Interaction of E-cadherin and PTEN Regulates Morphogenesis and Growth Arrest in Human Mammary Epithelial Cells
Marcia V. Fournier, Jimmie E. Fata, Katherine J. Martin, Paul Yaswen, and Mina J. Bissell
Cancer Research 2009; 69(10):4545–52
Approximately 50 percent of breast cancer patients have a mutation in—or loss of—at least one copy of the phosphatase and tensin homolog (PTEN), which is associated with poor outcome. PTEN acts as a tumor suppressor, in part by attenuating the activity of the PI3K, which often is increased in cancer and thus can act as an oncogene. PTEN has been shown also to interact with cell adhesion molecules such as b-catenin and E-cadherin to inhibit migration and proliferation and to shuttle between the nuclear and cytoplasmic compartments, although the significance of PTEN subcellular localization is not understood.
Bissell and colleagues used the three-dimensional, laminin-rich extracellular matrix gel model (lrECM) developed in her laboratory to culture nonmalignant human breast epithelial cells to investigate how PTEN and its localization affect proliferation and morphogenesis. In this model, HMECs form polarized, self-organizing structures that closely resemble structures in the mammary gland, and where signaling pathways respond to microenvironmental cues analogous to those that occur in mammary acini in vivo. The authors show that as acini begin to form, PTEN accumulates both in the cytoplasm and at cell-cell contacts where it colocalizes with the E-cadherin/b-catenin complex. Reduction of PTEN levels by shRNA prevents the formation of acini and disrupts growth arrest, while disruption of E-cadherin function reduces PTEN protein levels and inhibits its accumulation at cell-cell contacts. Exogenous introduction of E-cadherin in Skbr-3 breast cancer cells lacking endogenous E-cadherin causes induction of PTEN expression and accumulation at sites of cell-cell interactions. These results show that morphogenesis and the accompanied inhibition of cell proliferation in this physiologically relevant model of acinar polarity are dependent on E-cadherin–mediated up-regulation of PTEN and its interaction with E-cadherin.