Harold E. Varmus

Changes in gene expression during the development of mammary tumors in MMTV-Wnt-1transgenic mice (2005)

Huang, Shixia, Li, Yi, Chen, Yidong, Podsypanina, Katrina, Chamorro, Mario, Olshen, Adam B, ...

Abstract Background In human breast cancer normal mammary cells typically develop into hyperplasia, ductal carcinoma in situ , invasive cancer, and metastasis. The changes in gene expression...

KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib (2005)

William Pao, Theresa Y. Wang, Gregory J. Riely, Vincent A. Miller, Qiulu Pan, Marc Ladanyi, ...

Mutational analysis of the KRAS gene in lung cancer patients treated with two different kinase inhibitors suggests that tumors with KRAS mutations do not respond to these drugs.

KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib (2005)

William Pao, Theresa Y. Wang, Gregory J. Riely, Vincent A. Miller, Qiulu Pan, Marc Ladanyi, ...

Background Somatic mutations in the gene for the epidermal growth factor receptor (EGFR) are found in adenocarcinomas of the lung and are associated with sensitivity to the kinase inhibitors...

Evolution of somatic mutations in mammary tumors in transgenic mice is influenced by the inherited genotype (2004)

Podsypanina, Katrina, Li, Yi, Varmus, Harold E

Abstract Background MMTV-Wnt1 transgenic mice develop mammary hyperplasia early in development, followed by the appearance of solitary mammary tumors with a high proportion of cells expressing early...

Why PLoS Became a Publisher (2003)

Patrick O. Brown, Michael B. Eisen, Harold E. Varmus

Public Library of Science has grown from a grassroots movement to a nonprofit publisher, in order to catalyze change towards open-access publishing of the scientific literature.

Requirements for activation and RAFT localization of the T-lymphocyte kinase Rlk/Txk (2001)

Chamorro, Mario, Czar, Michael J, Debnath, Jayanta, Cheng, Genhong, Lenardo, Michael J, Varmus, Harold E, ...

Abstract Background The Tec family kinases are implicated in signaling from lymphocyte antigen receptors and are activated following phosphorylation by Src kinases. For most Tec kinases, this...

Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice (2001)

Li, Yi, Podsypanina, Katrina, Liu, Xiufan, Crane, Allison, Tan, Lee K, Parsons, Ramon, ...

Abstract Background Germline mutations in the tumor suppressor PTEN predispose human beings to breast cancer, and genetic and epigenetic alterations of PTEN are also detected in sporadic human breast...

Mammary-Specific Gene Transfer for Modeling Breast Cancer (1998)

Varmus, Harold E.

Several genetic alterations have been identified in breast cancer, yet the molecular mechanisms leading to breast tumorigenesis are unknown. In order to develop a mouse model system that can dissect...

Mammary-Specific Gene Transfer for Modeling Breast Cancer (1998)

Li, Yi, Varmus, Harold E.

In order to develop a mouse model system that allows for rapid assessment of genetic lesions involved in breast tumor development, we are adapting a somatic gene transfer system based on avian...

Gene localization by chromosome fractionation: Globin genes are on at least two chromosomes and three estrogen-inducible genes are on three chromosomes (1979)

Hughes, Stephen H., Stubblefield, Elton, Payvar, Farhang, Engel, James D., Dodgson, Jerry B., Spector, Deborah, ...

Chicken metaphase chromosomes were partially purified by rate zonal centrifugation, and DNA was prepared from each of the fractions of the sucrose gradient. The DNA was digested with various...

The murder of evil: a study of Charles Dickens (1961)

Varmus, Harold E.

This thesis is not available electronically or by photocopy. Please contact Archives and Special Collections at archives@amherst.edu for more information.

Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice

Holland, Eric C., Varmus, Harold E.

Basic fibroblast growth factor (bFGF) is overexpressed in most high-grade human gliomas, implying that it is involved in the pathogenesis of these tumors. To assess the biological effect of...

Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action

Finch, Paul W., He, Xi, Kelley, Michael J., Üren, Aykut, Schaudies, R. Paul, Popescu, Nicholas C., ...

Frizzled polypeptides are integral membrane proteins that recently were shown to function as receptors for Wnt signaling molecules. Here, we report the identification of a novel, secreted 36-kDa...

Membrane-anchored Plakoglobins Have Multiple Mechanisms of Action in Wnt Signaling

Klymkowsky, Michael W., Williams, Bart O., Barish, Grant D., Varmus, Harold E., Vourgourakis, Yanni E.

In Wnt signaling, β-catenin and plakoglobin transduce signals to the nucleus through interactions with TCF-type transcription factors. However, when plakoglobin is artificially engineered to...

Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a

Saint-Jeannet, Jean-Pierre, He, Xi, Varmus, Harold E., Dawid, Igor B.

Members of the Wnt family of signaling molecules are expressed differentially along the dorsal–ventral axis of the developing neural tube. Thus we asked whether Wnt factors are involved in...

Genetic Mapping of the Cloned Subgroup A Avian Sarcoma and Leukosis Virus Receptor Gene to the TVA Locus

Bates, Paul, Rong, Lijun, Varmus, Harold E., Young, John A. T., Crittenden, Lyman B.

A chicken gene conferring susceptibility to subgroup A avian sarcoma and leukosis viruses (ASLV-A) was recently identified by a gene transfer strategy. Classical genetic approaches had previously...

Development of an Avian Leukosis-Sarcoma Virus Subgroup A Pseudotyped Lentiviral Vector

Lewis, Brian C., Chinnasamy, Nachimuthu, Morgan, Richard A., Varmus, Harold E.

We are using avian leukosis-sarcoma virus (ALSV) vectors to generate mouse tumor models in transgenic mice expressing TVA, the receptor for subgroup A ALSV. Like other classical retroviruses, ALSV...

rlk/TXK Encodes Two Forms of a Novel Cysteine String Tyrosine Kinase Activated by Src Family Kinases

Debnath, Jayantha, Chamorro, Mario, Czar, Michael J., Schaeffer, Edward M., Lenardo, Michael J., Varmus, Harold E., ...

Rlk/Txk is a member of the BTK/Tec family of tyrosine kinases and is primarily expressed in T lymphocytes. Unlike other members of this kinase family, Rlk lacks a pleckstrin homology (PH) domain near...

Use of avian retroviral vectors to introduce transcriptional regulators into mammalian cells for analyses of tumor maintenance

Pao, William, Klimstra, David S., Fisher, Galen H., Varmus, Harold E.

A key issue in cancer biology is whether genetic lesions involved in tumor initiation or progression are required for tumor maintenance. This question can be addressed with mouse models that...

Why PLoS Became a Publisher

Brown, Patrick O, Eisen, Michael B, Varmus, Harold E

Public Library of Science has grown from a grassroots movement to a nonprofit publisher, in order to catalyze change towards open-access publishing of the scientific literature

Dexamethasone Induction of the Intracellular RNAs of Mouse Mammary Tumor Virus

Robertson, Donald L., Varmus, Harold E.

We have studied the kinetics of dexamethasone induction of mouse mammary tumor virus (MMTV) RNAs and proteins in virus-infected rat XC cells and GR mouse mammary tumor cells. A detectable increase in...

Proposal for Naming Host Cell-Derived Inserts in Retrovirus Genomes †

Coffin, John M., Varmus, Harold E., Bishop, J. Michael, Essex, Myron, Hardy, William D., Martin, G. Steven, ...

We propose a system for naming inserted sequences in transforming retroviruses (i.e., onc genes), based on using trivial names derived from a prototype strain of virus.

The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse model for pancreatic cancer

Lewis, Brian C., Klimstra, David S., Varmus, Harold E.

We have generated a mouse model for pancreatic cancer through the somatic delivery of oncogene-bearing avian retroviruses to mice that express TVA, the receptor for avian leukosis sarcoma virus...

Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells

Li, Yi, Welm, Bryan, Podsypanina, Katrina, Huang, Shixia, Chamorro, Mario, Zhang, Xiaomei, ...

Breast cancer is a genetically and clinically heterogeneous disease, and the contributions of different target cells and different oncogenic mutations to this heterogeneity are not well understood....

Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src−/− mutant mice

Schwartzberg, Pamela L., Xing, Lianping, Hoffmann, Oskar, Lowell, Clifford A., Garrett, Lisa, Boyce, Brendan F., ...

The Src tyrosine kinase has been implicated in a wide variety of signal transduction pathways, yet despite the nearly ubiquitous expression of c-src, src−/− mice show only one major...

A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice

Holland, Eric C., Hively, Wendy P., DePinho, Ronald A., Varmus, Harold E.

The epidermal growth factor receptor (EGFR) gene is amplified or mutated in 30%–50% of human gliobastoma multiforme (GBM). These mutations are associated usually with deletions of the INK4a–ARF...

Modeling mutations in the G1 arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a–ARF induces hyperploidy in cultured mouse astrocytes

Holland, Eric C., Hively, Wendy P., Gallo, Vittorio, Varmus, Harold E.

Nearly all human gliomas exhibit alterations in one of three genetic loci governing G1 arrest: INK4a–ARF, CDK4, or RB. To discern the roles of CDK4 amplification and INK4a–ARF loss in...

Use of DNA-DNA Annealing to Detect New Virus-Specific DNA Sequences in Chicken Embryo Fibroblasts After Infection by Avian Sarcoma Virus

Varmus, Harold E., Heasley, Suzanne, Bishop, J. Michael

Labeled, virus-specific DNA synthesized in vitro by the virion-associated polymerase of avian sarcoma virus (ASV) was used to measure virus-specific sequences in cell DNA in three ways: (i) by...

Integration of Deoxyribonucleic Acid Specific for Rous Sarcoma Virus after Infection of Permissive and Nonpermissive Hosts

Varmus, Harold E., Vogt, Peter K., Bishop, J. Michael

A relatively simple but stringent technique was developed to detect the integration of virus-specific DNA into the genomes of higher organisms. In both permissive (duck) and nonpermissive (mammalian)...

Detection of Avian Tumor Virus-Specific Nucleotide Sequences in Avian Cell DNAs

Varmus, Harold E., Weiss, Robin A., Friis, Robert R., Levinson, Warren, Bishop, J. Michael

The effect of unlabeled cellular DNA upon the reassociation kinetics of labeled double-stranded DNA made by DNA polymerase from avian tumor viruses has been used to measure virus-specific nucleotide...

Synthesis of Viral DNA in the Cytoplasm of Duck Embryo Fibroblasts and in Enucleated Cells after Infection by Avian Sarcoma Virus

Varmus, Harold E., Guntaka, Ramareddy V., Fan, Warner J. W., Heasley, Suzanne, Bishop, J. Michael

Two lines of evidence indicate that synthesis of viral DNA occurs in the cytoplasm of duck embryo fibroblasts infected with avian sarcoma virus: (i) viral DNA is detected first in the cytoplasmic...

env Gene of Chicken RNA Tumor Viruses: Extent of Conservation in Cellular and Viral Genomes

Fujita, Donald J., Tal, Jacov, Varmus, Harold E., Bishop, J. Michael

The env gene of avian sarcoma-leukosis viruses codes for envelope glycoproteins that determine viral host range, antigenic specificity, and interference patterns. We used molecular hybridization to...

FGF-20 and DKK1 are transcriptional targets of β-catenin and FGF-20 is implicated in cancer and development

Chamorro, Mario N, Schwartz, Donald R, Vonica, Alin, Brivanlou, Ali H, Cho, Kathleen R, Varmus, Harold E

β-catenin is the major effector of the canonical Wnt signaling pathway. Mutations in components of the pathway that stabilize β-catenin result in augmented gene transcription and play a major role...

KRAS Mutations and Primary Resistance of Lung Adenocarcinomas to Gefitinib or Erlotinib

Pao, William, Wang, Theresa Y, Riely, Gregory J, Miller, Vincent A, Pan, Qiulu, Ladanyi, Marc, ...

Mutational analysis of the KRAS gene in lung cancer patients treated with two different kinase inhibitors suggests that tumors with KRAS mutations do not respond to these drugs

The Absence of p53 Promotes Metastasis in a Novel Somatic Mouse Model for Hepatocellular Carcinoma†

Lewis, Brian C., Klimstra, David S., Socci, Nicholas D., Xu, Su, Koutcher, Jason A., Varmus, Harold E.

We have generated a mouse model for hepatocellular carcinoma using somatic delivery of oncogene-bearing avian retroviral vectors to the liver cells of mice expressing the viral receptor TVA under the...

Changes in gene expression during the development of mammary tumors in MMTV-Wnt-1 transgenic mice

Huang, Shixia, Li, Yi, Chen, Yidong, Podsypanina, Katrina, Chamorro, Mario, Olshen, Adam B, ...

cDNA microarray-derived expression profiles of MMTV-Wnt-1 and MMTV-Neu transgenic mice reveal several hundred genes to be differentially expressed at each stage of breast tumor development.

Genetic evidence for a role for Src family kinases in TNF family receptor signaling and cell survival

Xing, Lianping, Venegas, Ana M., Chen, Amy, Garrett-Beal, Lisa, Boyce, Brendan F., Varmus, Harold E., ...

Mutant src−/− mice have osteopetrosis resulting from defective osteoclasts, the cells that resorb bone. However, signaling pathways involving Src family members in osteoclasts remain unclear. We...

Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes

Fisher, Galen H., Wellen, Shari L., Klimstra, David, Lenczowski, Joi M., Tichelaar, Jay W., Lizak, Martin J., ...

To investigate the role of an activated K-Ras gene in the initiation and maintenance of lung adenocarcinomas, we developed transgenic mice that express murine K-Ras4bG12D under the control of...

Lung adenocarcinomas induced in mice by mutant EGF receptors foundin human lung cancers respondto a tyrosine kinase inhibitor orto down-regulation of the receptors

Politi, Katerina, Zakowski, Maureen F., Fan, Pang-Dian, Schonfeld, Emily A., Pao, William, Varmus, Harold E.

Somatic mutations in exons encoding the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene are found in human lung adenocarcinomas and are associated with sensitivity to the...

Basic fibroblast growth factor induces cell migration and proliferation after glia-specific gene transfer in mice

Holland, Eric C., Varmus, Harold E.

Basic fibroblast growth factor (bFGF) is overexpressed in most high-grade human gliomas, implying that it is involved in the pathogenesis of these tumors. To assess the biological effect of...

Purification and molecular cloning of a secreted, Frizzled-related antagonist of Wnt action

Finch, Paul W., He, Xi, Kelley, Michael J., Üren, Aykut, Schaudies, R. Paul, Popescu, Nicholas C., ...

Frizzled polypeptides are integral membrane proteins that recently were shown to function as receptors for Wnt signaling molecules. Here, we report the identification of a novel, secreted 36-kDa...

Membrane-anchored Plakoglobins Have Multiple Mechanisms of Action in Wnt Signaling

Klymkowsky, Michael W., Williams, Bart O., Barish, Grant D., Varmus, Harold E., Vourgourakis, Yanni E.

In Wnt signaling, β-catenin and plakoglobin transduce signals to the nucleus through interactions with TCF-type transcription factors. However, when plakoglobin is artificially engineered to...

Regulation of dorsal fate in the neuraxis by Wnt-1 and Wnt-3a

Saint-Jeannet, Jean-Pierre, He, Xi, Varmus, Harold E., Dawid, Igor B.

Members of the Wnt family of signaling molecules are expressed differentially along the dorsal–ventral axis of the developing neural tube. Thus we asked whether Wnt factors are involved in...

Genetic Mapping of the Cloned Subgroup A Avian Sarcoma and Leukosis Virus Receptor Gene to the TVA Locus

Bates, Paul, Rong, Lijun, Varmus, Harold E., Young, John A. T., Crittenden, Lyman B.

A chicken gene conferring susceptibility to subgroup A avian sarcoma and leukosis viruses (ASLV-A) was recently identified by a gene transfer strategy. Classical genetic approaches had previously...

Development of an Avian Leukosis-Sarcoma Virus Subgroup A Pseudotyped Lentiviral Vector

Lewis, Brian C., Chinnasamy, Nachimuthu, Morgan, Richard A., Varmus, Harold E.

We are using avian leukosis-sarcoma virus (ALSV) vectors to generate mouse tumor models in transgenic mice expressing TVA, the receptor for subgroup A ALSV. Like other classical retroviruses, ALSV...

rlk/TXK Encodes Two Forms of a Novel Cysteine String Tyrosine Kinase Activated by Src Family Kinases

Debnath, Jayantha, Chamorro, Mario, Czar, Michael J., Schaeffer, Edward M., Lenardo, Michael J., Varmus, Harold E., ...

Rlk/Txk is a member of the BTK/Tec family of tyrosine kinases and is primarily expressed in T lymphocytes. Unlike other members of this kinase family, Rlk lacks a pleckstrin homology (PH) domain near...

Use of avian retroviral vectors to introduce transcriptional regulators into mammalian cells for analyses of tumor maintenance

Pao, William, Klimstra, David S., Fisher, Galen H., Varmus, Harold E.

A key issue in cancer biology is whether genetic lesions involved in tumor initiation or progression are required for tumor maintenance. This question can be addressed with mouse models that...

Why PLoS Became a Publisher

Brown, Patrick O, Eisen, Michael B, Varmus, Harold E

Public Library of Science has grown from a grassroots movement to a nonprofit publisher, in order to catalyze change towards open-access publishing of the scientific literature

Dexamethasone Induction of the Intracellular RNAs of Mouse Mammary Tumor Virus

Robertson, Donald L., Varmus, Harold E.

We have studied the kinetics of dexamethasone induction of mouse mammary tumor virus (MMTV) RNAs and proteins in virus-infected rat XC cells and GR mouse mammary tumor cells. A detectable increase in...

Proposal for Naming Host Cell-Derived Inserts in Retrovirus Genomes †

Coffin, John M., Varmus, Harold E., Bishop, J. Michael, Essex, Myron, Hardy, William D., Martin, G. Steven, ...

We propose a system for naming inserted sequences in transforming retroviruses (i.e., onc genes), based on using trivial names derived from a prototype strain of virus.

The c-myc and PyMT oncogenes induce different tumor types in a somatic mouse model for pancreatic cancer

Lewis, Brian C., Klimstra, David S., Varmus, Harold E.

We have generated a mouse model for pancreatic cancer through the somatic delivery of oncogene-bearing avian retroviruses to mice that express TVA, the receptor for avian leukosis sarcoma virus...

Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells

Li, Yi, Welm, Bryan, Podsypanina, Katrina, Huang, Shixia, Chamorro, Mario, Zhang, Xiaomei, ...

Breast cancer is a genetically and clinically heterogeneous disease, and the contributions of different target cells and different oncogenic mutations to this heterogeneity are not well understood....

Genetic evidence for a role for Src family kinases in TNF family receptor signaling and cell survival

Xing, Lianping, Venegas, Ana M., Chen, Amy, Garrett-Beal, Lisa, Boyce, Brendan F., Varmus, Harold E., ...

Mutant src−/− mice have osteopetrosis resulting from defective osteoclasts, the cells that resorb bone. However, signaling pathways involving Src family members in osteoclasts remain unclear. We...

Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes

Fisher, Galen H., Wellen, Shari L., Klimstra, David, Lenczowski, Joi M., Tichelaar, Jay W., Lizak, Martin J., ...

To investigate the role of an activated K-Ras gene in the initiation and maintenance of lung adenocarcinomas, we developed transgenic mice that express murine K-Ras4bG12D under the control of...

Rescue of osteoclast function by transgenic expression of kinase-deficient Src in src−/− mutant mice

Schwartzberg, Pamela L., Xing, Lianping, Hoffmann, Oskar, Lowell, Clifford A., Garrett, Lisa, Boyce, Brendan F., ...

The Src tyrosine kinase has been implicated in a wide variety of signal transduction pathways, yet despite the nearly ubiquitous expression of c-src, src−/− mice show only one major...

A constitutively active epidermal growth factor receptor cooperates with disruption of G1 cell-cycle arrest pathways to induce glioma-like lesions in mice

Holland, Eric C., Hively, Wendy P., DePinho, Ronald A., Varmus, Harold E.

The epidermal growth factor receptor (EGFR) gene is amplified or mutated in 30%–50% of human gliobastoma multiforme (GBM). These mutations are associated usually with deletions of the INK4a–ARF...

Modeling mutations in the G1 arrest pathway in human gliomas: overexpression of CDK4 but not loss of INK4a–ARF induces hyperploidy in cultured mouse astrocytes

Holland, Eric C., Hively, Wendy P., Gallo, Vittorio, Varmus, Harold E.

Nearly all human gliomas exhibit alterations in one of three genetic loci governing G1 arrest: INK4a–ARF, CDK4, or RB. To discern the roles of CDK4 amplification and INK4a–ARF loss in...