Abstract: Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

Abstract: The invention provides methods and materials related to Bcl2L12 polypeptides and the biological activities of Bcl2L12 polypeptides. For example, the invention provides methods and materials related to identifying activators and inhibitors of Bcl2L12 polypeptide activities such as the ability to block apoptosis and promote cell growth and transformation. The invention also provides methods and materials for treating mammals having cancer.

Abstract: This invention provides for murine telomerase reverse transcriptase (mTERT) enzyme proteins and nucleic acids, including methods for isolating and expressing these nucleic acids and proteins, which have application to the control of cell proliferation and aging, including the control of age-related diseases, such as cancer.

Abstract: The present invention is based, at least in part, on the generation of an animal model of pancreatic adenocarcinoma which recapitulates the genetic and histological features of human pancreatic adenocarcinoma, including the initiation, maintenance, and progression of the disease. Accordingly, the present invention provides animal models of cancer, e.g., pancreatic adenocarcinoma, wherein an activating mutation of Kras has been introduced, and any one or more known or unknown tumor suppressor genes or loci, e.g., Ink4a/Arf, Ink4a, Arf, p53, Smad4/Dpc, Lkb1, Brca2, or Mlh1, have been misexpressed, e.g., have been misexpressed leading to decreased expression or non-expression. The animal models of the invention may be used, for example, to identify biomarkers of pancreatic cancer, to identify agents for the treatment or prevention of pancreatic cancer, and to evaluate the effectiveness of potential therapeutic agents.

Abstract: The invention relates to modulation of LKB1 or AMP kinase protein activity for treating disorders including diabetes and cancer. The invention also relates to screening for agents that modulate the activity of LKB1 or AMP kinase protein, which are useful in the treatment of diabetes and cancer, as well as preparing compounds for treatment of diabetes and cancer.

Abstract: The invention provides methods and materials for identifying and characterizing genes related to phenotypes such as cancer and cell survivability. Also provided in the invention are cells and transgenic, non-human mammals that can be used in these methods.

Abstract: The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating human cancer. A variety of chromosomal regions (MCRs) and markers corresponding thereto, are provided, wherein alterations in the copy number of one or more of the MCRs and/or alterations in the amount, structure, and/or activity of one or more of the markers is correlated with the presence of cancer.

Abstract: Chimeric nonhuman mammals useful as inducible spontaneous cancer models are disclosed. The nonhuman mammals are obtained by introducing one or more genetically modified embryonic stem (ES) cells into an early stage embryo, and then implanting the manipulated embryo into a surrogate mother. The ES cells contain a recombinant oncogene, and also may contain a genetic mutation that deletes or inactivates a tumor suppressor gene. Models of different types of cancer are produced by introducing different combinations of genetic mutations into the ES cells that are introduced into the early stage embryo.

Abstract: A non-human mammal having incorporated into its genome an expression construct in which nucleic acid encoding and oncogene is operably linked to an inducible promoter; the mammal further has a genetic mutation that causes it to have an increased susceptibility to cancer.

Abstract: The invention provides methods and materials related to Bcl2L12 polypeptides and the biological activities of Bcl2L12 polypeptides. For example, the invention provides methods and materials related to identifying activators and inhibitors of Bcl2L12 polypeptide activities such as the ability to block apoptosis and promote cell growth and transformation. The invention also provides methods and materials for treating mammals having cancer.

Abstract: The present invention provides a novel method of inhibiting the growth of tumor cells based upon the discovery that p19ARF acts as a suppressor of oncogenic transformation by binding to the MDM2 oncoprotein and blocking MDM2's ability to target associated proteins, such as p53 and Rb, for proteosomal degradation. The method provided by the present invention inhibits the growth of a tumor cell by administering to the cell an effective amount of p19ARF or a mimetic thereof, and p53 to inhibit the growth of the tumor cell. Also provided by the present invention are pharmaceutical composition comprising p19ARF or a mimetic thereof, and/or p53.

Abstract: This invention provides for murine telomerase reverse transcriptase (mTERT) enzyme proteins and nucleic acids, including methods for isolating and expressing these nucleic acids and proteins, which have application to the control of cell proliferation and aging, including the control of age-related diseases, such as cancer.

Abstract: A non-human mammal having incorporated into its genome an expression construct in which nucleic acid encoding and oncogene is operably linked to an inducible promoter; the mammal further has a genetic mutation that causes it to have an increased susceptibility to cancer.

Abstract: The present invention provides a novel MHRII-associated protein designated MHRII-AP62 and antibodies immunoreactive with the MHRII-AP62 protein. Also provided are kits containing these antibodies and methods of using the antibodies for the detection of the MHRII-AP62 protein. The present invention also provides for a nucleic acid encoding the MHRII-AP62 protein and nucleic acid probes for use in the detection of the MHRII-AP62 protein. Further provided by the present invention are agents that mimic the activity of the MHRII-AP62 protein by binding to the MHRII, agents that inhibit the activity of the MHRII-AP62 protein by binding to the MHRII-AP62 protein, or by binding to the nucleic acid encoding the MHRII-AP62 protein, and methods of using these agents to treat cancer and cancer causing diseases.

Abstract: The invention provides chimeric non-human animals, methods for making and using chimeric non-human animals, isolated stem cells, and methods for identifying agents that reduces cancer in a non-human animal. For example, the invention relates to using stem cells to make chimeric non-human animals having cancer or the ability to develop cancer. Such animals can be used to evaluate tumorigenesis, tumor maintenance, and tumor regression in vivo. In addition, the chimeric non-human animals provided herein can be used to identify agents that reduce or prevent tumor formation or growth in vivo.

Abstract: A non-human mammal having incorporated into its genome an expression construct in which nucleic acid encoding an oncogene is operably linked to an inducible promoter; the mammal further has a genetic mutation that causes it to have an increased susceptibility to cancer.

Abstract: The present invention provides a novel method of inhibiting the growth of tumor cells based upon the discovery that p19ARF acts as a suppressor of oncogenic transformation by binding to the MDM2 oncoprotein and blocking MDM2's ability to target associated proteins, such as p53 and Rb, for proteosomal degradation. The method provided by the present invention inhibits the growth of a tumor cell by administering to the cell an effective amount of p19ARF or a mimetic thereof, and p53 to inhibit the growth of the tumor cell. Also provided by the present invention are pharmaceutical composition comprising p19ARF or a mimetic thereof, and/or p53.

Abstract: The present invention provides a novel method of inhibiting the growth of tumor cells based upon the discovery that p19ARF acts as a suppressor of oncogenic transformation by binding to the MDM2 oncoprotein and blocking MDM2's ability to target associated proteins, such as p53 and Rb, for proteosomal degradation. The method provided by the present invention inhibits the growth of a tumor cell by administering to the cell an effective amount of p19ARF or a mimetic thereof, and p53 to inhibit the growth of the tumor cell. Also provided by the present invention are pharmaceutical composition comprising p19ARF or a mimetic thereof, and/or p53.

Abstract: The invention provides methods and materials for identifying and characterizing genes related to phenotypes such as cancer and cell survivability. Also provided in the invention are cells and transgenic, non-human mammals that can be used in these methods.

Abstract: The present invention provides a novel method of inhibiting the growth of tumor cells based upon the discovery that p19ARF acts as a suppressor of oncogenic transformation by binding to the MDM2 oncoprotein and blocking MDM2's ability to target associated proteins, such as p53 and Rb, for proteosomal degradation. The method provided by the present invention inhibits the growth of a tumor cell by administering to the cell an effective amount of p19ARF or a mimetic thereof, and p53 to inhibit the growth of the tumor cell. Also provided by the present invention are pharmaceutical composition comprising p19ARF or a mimetic thereof, and/or p53.