Abstract: A signature for breast cancer tissue derived from a patient is established that is indicative of the virulence and risk of lung metastasis by determining the expression levels to define a sample signature, and comparing this sample signature to a reference signature. The reference signature defines a standard expression level for each gene and a significant change direction, i.e., either overexpressed or underexpressed. A sample signature that differs from the reference signature in the significant change direction for a predetermined number of the genes tested is indicative of a significant risk of lung metastasis. This determination is used to define appropriate treatment and monitoring options for the patient.

Abstract: The cytokine TGF?, in the tumor microenvironment, primes cancer cells for metastasis to the lungs. TGF? response status (TBRS) can be determined by comparing expression levels of a panel of genes from cancer cells to the expression levels of the same genes in epithelial cell lines before and after induction with TGF?. A TGF? gene response signature reveals a clinical association between TGF? activity in primary estrogen receptor negative (ER?) tumors and risk of lung metastasis. Further, combining the gene signature of the present invention with the known lung metastasis signature (LMS) increases the predictive value of the LMS considerably.

Abstract: This invention relates, e.g., to a method for identifying an agent that inhibits a metastatic cell (e.g. that inhibits cancer metastasis), comprising measuring the amount of seeding of a tumor by a detectably labeled, metastatic cell, in a subject, in the presence and absence of a putative agent, wherein the amount of seeding by the metastatic cell is proportional to the metastatic potential of the cell, and wherein a significant amount of inhibition of the seeding by the putative agent indicates that the putative agent is effective to inhibit the metastatic cell (e, g, cancer metastasis). Also described are kits suitable for performing methods of the invention.

Abstract: Two sets of genes and their encoded proteins, one set of 17 genes/proteins and one set of 18 genes/proteins that can be used in predicting the risk of cancer metastasis to the brain, and as a screening assay to identify the suitable treatments for brain metastases. Genes/proteins within the sets that are found to be differentially expressed relative to a control value are suitable targets for therapy.

Abstract: A signature for breast cancer tissue derived from a patient is established that is indicative of the virulence and risk of lung metastasis by determining the expression levels to define a sample signature, and comparing this sample signature to a reference signature. The reference signature defines a standard expression level for each gene and a significant change direction, i.e., either overexpressed or underexpressed. A sample signature that differs from the reference signature in the significant change direction for a predetermined number of the genes tested is indicative of a significant risk of lung metastasis. This determination is used to define appropriate treatment and monitoring options for the patient.

Abstract: This invention relates, e.g., to a method for identifying an agent that inhibits a metastatic cell (e.g. that inhibits cancer metastasis), comprising measuring the amount of seeding of a tumor by a detectably labeled, metastatic cell, in a subject, in the presence and absence of a putative agent, wherein the amount of seeding by the metastatic cell is proportional to the metastatic potential of the cell, and wherein a significant amount of inhibition of the seeding by the putative agent indicates that the putative agent is effective to inhibit the metastatic cell (e, g, cancer metastasis). Also described are kits suitable for performing methods of the invention.

Abstract: Signal transduction by the TGF-&bgr; family involves sets of receptor serine/threonine kinases, Smad proteins that act as receptor substrates, and Smad-associated transcription factors that target specific genes. Discrete structural elements were identified that dictate the selective interactions between receptors and Smads and between Smads and transcription factors in the TGF-&bgr; and BMP pathways. A cluster of four residues in the L45 loop of the type I receptor kinase domain, and a matching set of two residues in the L3 loop of the Smad C-terminal domain establish the specificity of receptor-Smad interactions. A cluster of residues in the highly exposed &agr;-helix 2 of the Smad C-terminal domain specify the interaction with the DNA-binding factor Fast1 and, as a result, the gene responses mediated by the pathway. By establishing specific interactions, these determinants keep the TGF-&bgr; and BMP pathways segregated from each other.

Abstract: An isolated protein designated p27 is disclosed. The p27 protein has an apparent molecular weight of about 27 kD, and is capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. A nucleic acid sequence encoding p27 protein is disclosed, as well as a method for producing p27 in cultured cells. in vitro assays for discovering agents which effect the activity of p27 are also provided. Methods of diagnosing and treating hypoproliferative and hyperproliferative disorders are provided.

Abstract: An isolated protein designated p27 is disclosed. The p27 protein has an apparent molecular weight of about 27 kD, and is capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. A nucleic acid sequence encoding p27 protein is disclosed, as well as a method for producing p27 in cultured cells. In vitro assays for discovering agents which affect the activity of p27 are also provided. Methods of diagnosing and treating hypoproliferative disorders are provided.

Abstract: An isolated protein designated p27 is disclosed. The p27 protein has an apparent molecular weight of about 27 kD, and is capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. A nucleic acid sequence encoding p27 protein is disclosed, as well as a method for producing p27 in cultured cells. In vitro assays for discovering agents which affect the activity of p27 are also provided. Methods of diagnosing and treating hypoproliferative disorders are provided.

Abstract: The subject invention is directed to the discovery of a protein involved in regulation of cell-cycle progression, and includes reagents and methods related thereto.

Abstract: The subject invention provides an isolated protein having an apparent molecular weight of about 27 kD and capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. The subject invention further provides an isolated antibody and a purified preparation of polyclonal and monoclonal antibodies which are specifically immunoreactive with a p27 protein. The subject invention further provides a kit for detecting a p27 protein.

Abstract: This invention provides an isolated nucleic acid molecule encoding a mammalian p57.sup.KIP2. This invention also provides vectors comprising the isolated nucleic acid molecule encoding a mammalian p57.sup.KIP2. This invention further provides a host vector system for the production of a mammalian p57.sup.KIP2. This invention also provides probes for the isolated nucleic acid molecule encoding a mammalian p57.sup.KIP2. This invention provides antibodies directed against a mammalian p57.sup.KIP2. This invention also provides transgenic animals comprising isolated nucleic acid molecules encoding a mammalian p57.sup.KIP2. Finally, this invention provides different uses of the mammalian p57.sup.KIP2.

Abstract: This invention provides a novel purified TGF-.beta.-binding glycoprotein, endoglin, an isolated nucleic acid molecule that encodes an amino acid sequence corresponding to the TGF-.beta.-binding glycoprotein, soluble endoglin-derived polypeptide, and fragments thereof. A pharmaceutical composition which comprises the endoglin-derived polypeptide purified by applicants or produced by applicants' recombinant methods and a pharmaceutically acceptable carrier is further provided as well as methods of treating patients which comprise administering to the patient the pharmaceutical composition of this invention.

Abstract: This invention provides a novel purified TGF-.beta.-binding glycoprotein, endoglin, an isolated nucleic acid molecule that encodes an amino acid sequence corresponding to the TGF-.beta.-binding glycoprotein, soluble endoglin-derived polypeptide, and fragments thereof. A pharmaceutical composition which comprises the endoglin-derived polypeptide purified by applicants or produced by applicants' recombinant methods and a pharmaceutically acceptable carrier is further provided as well as methods of treating patients which comprise administering to the patient the pharmaceutical composition of this invention.

Abstract: This invention provides a novel purified TGF-.beta.-binding glycoprotein, endoglin, an isolated nucleic acid molecule that encodes an amino acid sequence corresponding to the TGF-.beta.-binding glycoprotein, soluble endoglin-derived polypeptide, and fragments thereof. A pharmaceutical composition which comprises the endoglin-derived polypeptide purified by applicants or produced by applicants' recombinant methods and a pharmaceutically acceptable carrier is further provided as well as methods of treating patients which comprise administering to the patient the pharmaceutical composition of this invention.

Abstract: The subject invention provides an isolated protein having an apparent molecular weight of about 27 kD and capable of binding to and inhibiting the activation of a cyclin E-Cdk2 complex. The subject invention further provides a recombinant nucleic acid molecule which encodes the p27 protein of the subject invention, and related vectors and host vector systems. The subject invention further provides a method for producing the p27 protein of the subject invention using the host vector system. The subject invention further provides methods of determining whether an agent is capable of specifically inhibiting or enhancing the ability of p27 protein to inhibit the activation of cyclin E-Cdk2 complex. Finally, this subject invention provides different uses of the isolated protein, the recombinant nucleic acid molecule encoding the isolated protein and the agent capable of inhibiting or enchancing the ability of p27 protein to inhibit the activation of cyclin E-Cdk2 complex.