We have shown previously that c-Src null epithelial cells are unable to respond to estrogenic stimulation [1]. In addition, c-Src recruitment to ErbB-2 catalytic domain could be involved in the...
Andrechek, Eran R., Muller, William J.
In human breast cancer, 20 to 30% of human breast cancers amplify and overexpress the Neu proto-oncogene. To fully elucidate the role of this gene in normal development and breast cancer, we have...
Hutchinson, John N. G., Muller, William J.
Activation of Akt-1 by the phosphatidylinositol 3'-OH kinase (PI3K) results in the inhibition of pro-apoptotic signals and the promotion of survival and proliferation signals. Transgenic mice...
The primary objective of this proposal is to elucidate the role of the phosphadityl inositol 3' kinase (PI-3' kinase) and its coupled downstream signaling pathways in the induction of mammary...
Andrechek, Eran R, Muller, William J
Abstract The ability of growth factors and their cognate receptors to induce mammary epithelial proliferation and differentiation is dependent on their ability to activate a number of specific signal...
Transgenic mice expressing either the neu or TGFa in the mammary epithelium develop focal mammary tumours that occur only after a long latency period. Because the epidermal growth factor receptor and...
Elevated expression of members of the epidermal growth factor receptor (EGFR) family has been frequently observed in a large number of sporadic breast cancers. For example, overexpression and...
The major focus of DOD sponsored research program is to assess the role of the phosphadityl inositol 3f (PI-3f) and Akt-1 kinases in mammary tumorigenesis and metastasis. Although evidence suggests...
The Role of the Integrin-Linked Kinase in Mammary Gland Tumorigenesis and Metastasis (1998)
The primary objective of this proposal is to elucidate the role of the integrin linked kinase in the induction of mammary tumors. To accomplish this, we have generated transgenic mice that express a...
The Akt/PKB serine/threonine kinase plays roles in coupling growth factor receptors to cell survival pathways. Although evidence suggests roles for phosphatidylinositol 3'-OH Kinase (PI3K) and Akt in...
The Role of the Integrin-Linked Kinase (ILK) in Mammary Gland Tumorigenesis and Metastasis (1998)
The major objective of our DOD sponsored research program is to assess the role od the integrin linked kinase in mammary tumorigenesis and metastasis. Based on previous observation that ILK is...
The molecular basis for progression of breast cancer from hormone dependence to hormone independence remains one of the critical issues in this prevalent but poorly understood disease. The principle...
Chan, Richard, Muller, William J.
The ErbB-2/Neu receptor tyrosine kinase plays important roles in development and disease. To genetically dissect the ErbB-2 mediated signaling pathway in vivo, we have generated neu cDNA knock-in...
Chan, Richard, Muller, William J.
The ErbB2 receptor tyronsine kinase plays important roles in development and disease. To investigate the developmental roles of ErbB2 mediated signaling in vivo, we have generated a series of erbB2...
ER(alpha) and ErbB-2 Cross-Talk in Mammary Tumorigenesis and Metastasis (1998)
The interaction between growth factor and steroid hormone receptors may play a critical role in the breast cancer progression. The principle objective of this proposal is to elucidate the in vivo...
ERalpha and ErbB-2 Cross-Talk in Mammary Turmorigenesis and Metastasis (1998)
The induction of human breast cancer involves the complex interplay of hormones and growth factor Receptors. The major focus of our DOD sponsored research program is to investigate the interaction of...
Transgenic mice expressing an activated neu oncogene in the mammary epithelium develop metastatic mammary tumors within a short latency period. Given our recent observations suggesting that...
Amplification of the neu/erbB-2 oncogene in a mouse model of mammary tumorigenesis
Andrechek, Eran R., Hardy, William R., Siegel, Peter M., Rudnicki, Michael A., Cardiff, Robert D., Muller, William J.
The neu (c-erbB-2, Her-2) protooncogene is amplified and overexpressed in 20–30% of human breast cancers. Although transgenic mouse models have illustrated the role of Neu in the induction of...
Pützer, Brigitte M., Hitt, Mary, Muller, William J., Emtage, Peter, Gauldie, Jack, Graham, Frank L.
Stimulation of antitumor immune mechanisms is the primary goal of cancer immunotherapy, and accumulating evidence suggests that effective alteration of the host–tumor relationship involves...
Rauh, Michael J., Blackmore, Valerie, Andrechek, Eran R., Tortorice, Christopher G., Daly, Roger, Lai, Venus Ka-Man, ...
The Grb2 and Shc adapter proteins play critical roles in coupling activated growth factor receptors to several cellular signaling pathways. To assess the role of these molecules in mammary epithelial...
Lee, Richard J., Albanese, Chris, Fu, Maofu, D'Amico, Mark, Lin, Bing, Watanabe, Genichi, ...
The neu (c-erbB-2) proto-oncogene encodes a tyrosine kinase receptor that is overexpressed in 20 to 30% of human breast tumors. Herein, cyclin D1 protein levels were increased in mammary tumors...
Dankort, David, Maslikowski, Bart, Warner, Neil, Kanno, Nubufumi, Kim, Harold, Wang, Zhixiang, ...
Amplification of the Neu (ErbB-2 or HER-2) receptor tyrosine kinase occurs in 20 to 30% of human mammary carcinomas, correlating with a poor clinical prognosis. We have previously demonstrated that...
Hutchinson, John, Jin, Jing, Cardiff, Robert D., Woodgett, Jim R., Muller, William J.
Activation of Akt by the phosphatidylinositol 3′-OH kinase (PI3K) results in the inhibition of proapoptotic signals and the promotion of survival signals (L. P. Kane et al., Curr. Biol....
Webster, Marc A., Hutchinson, John N., Rauh, Michael J., Muthuswamy, Senthil K., Anton, Martina, Tortorice, Christopher G., ...
Transgenic mice expressing the polyomavirus (PyV) middle T antigen (MT) develop multifocal mammary tumors which frequently metastasize to the lung. The potent transforming activity of PyV MT is...
Genetic instability favoring transversions associated with ErbB2-induced mammary tumorigenesis
Liu, Shiquan, Liu, Wenjing, Jakubczak, John L., Erexson, Gregory L., Tindall, Kenneth R., Chan, Richard, ...
It has been argued that genetic instability is required to generate the myriad mutations that fuel tumor initiation and progression and, in fact, patients with heritable cancer susceptibility...
Nguyen, AnhCo, Burack, W. Richard, Stock, Jeffrey L., Kortum, Robert, Chaika, Oleg V., Afkarian, Maryam, ...
While scaffold proteins are thought to be key components of signaling pathways, their exact function is unknown. By preassembling multiple components of signaling cascades, scaffolds are predicted to...
ErbB2 Is Required for Muscle Spindle and Myoblast Cell Survival
Andrechek, Eran R., Hardy, William R., Girgis-Gabardo, Adele A., Perry, Robert L. S., Butler, Richard, Graham, Frank L., ...
Signaling mediated by ErbB2 is thought to play a critical role in numerous developmental processes. However, due to the embryonic lethality associated with the germ line inactivation of erbB2, its...
The Catalytic Activity of the ErbB-2 Receptor Tyrosine Kinase Is Essential for Embryonic Development
Chan, Richard, Hardy, William R., Laing, Michael A., Hardy, Sarah E., Muller, William J.
Activation of the epidermal growth factor receptor (EGFR) family is thought to play a critical role in both embryogenesis and oncogenesis. The diverse biological activities of the EGFR family are...
Andrechek, Eran R, Muller, William J
The ability of growth factors and their cognate receptors to induce mammary epithelial proliferation and differentiation is dependent on their ability to activate a number of specific signal...
Williams, Terence M., Cheung, Michelle W.-C., Park, David S., Razani, Babak, Cohen, Alex W., Muller, William J., ...
Caveolin-1 is the principal structural component of caveolae microdomains, which represent a subcompartment of the plasma membrane. Several independent lines of evidence support the notion that...
Siegel, Peter M., Shu, Weiping, Cardiff, Robert D., Muller, William J., Massagué, Joan
The influence of transforming growth factor β (TGF-β) signaling on Neu-induced mammary tumorigenesis and metastasis was examined with transgenic mouse models. We generated mice expressing an...
De Candia, Paola, Solit, David B., Giri, Dilip, Brogi, Edi, Siegel, Peter M., Olshen, Adam B., ...
Id proteins bind basic helix–loop–helix transcription factors and function as dominant negative inhibitors of gene expression. Id1 and Id3 are required for the recruitment of bone marrow-derived...
Ets2-Dependent Stromal Regulation of Mouse Mammary Tumors
Man, Albert K., Young, Lawrence J. T., Tynan, John A., Lesperance, Jacqueline, Egeblad, Mikala, Werb, Zena, ...
The Ets2 transcription factor is regulated by mitogen-activated protein (MAP) kinase phosphorylation of a single threonine residue. We generated by gene targeting a single codon mutation in Ets2...
Saucier, Caroline, Khoury, Hanane, Lai, Ka-Man Venus, Peschard, Pascal, Dankort, David, Naujokas, Monica A., ...
The etiology and progression of a variety of human malignancies are linked to the deregulation of receptor tyrosine kinases (RTKs). To define the role of RTK-dependent signals in various oncogenic...
Andrechek, Eran R., Hardy, William R., Laing, Michael A., Muller, William J.
We have previously shown that mammary epithelial specific expression of the activated erbB2 allele under the control of the endogenous promoter in mice resulted in the formation of mammary...
HGF Converts ErbB2/Neu Epithelial Morphogenesis to Cell Invasion
Khoury, Hanane, Naujokas, Monica A., Zuo, Dongmei, Sangwan, Veena, Frigault, Melanie M., Petkiewicz, Stephanie, ...
Activation of the hepatocyte growth factor receptor Met induces a morphogenic response and stimulates the formation of branching tubules by Madin-Darby canine kidney (MDCK) epithelial cells in...
Amplification of the neu/erbB-2 oncogene in a mouse model of mammary tumorigenesis
Andrechek, Eran R., Hardy, William R., Siegel, Peter M., Rudnicki, Michael A., Cardiff, Robert D., Muller, William J.
The neu (c-erbB-2, Her-2) protooncogene is amplified and overexpressed in 20–30% of human breast cancers. Although transgenic mouse models have illustrated the role of Neu in the induction of...
Pützer, Brigitte M., Hitt, Mary, Muller, William J., Emtage, Peter, Gauldie, Jack, Graham, Frank L.
Stimulation of antitumor immune mechanisms is the primary goal of cancer immunotherapy, and accumulating evidence suggests that effective alteration of the host–tumor relationship involves...
Rauh, Michael J., Blackmore, Valerie, Andrechek, Eran R., Tortorice, Christopher G., Daly, Roger, Lai, Venus Ka-Man, ...
The Grb2 and Shc adapter proteins play critical roles in coupling activated growth factor receptors to several cellular signaling pathways. To assess the role of these molecules in mammary epithelial...
Lee, Richard J., Albanese, Chris, Fu, Maofu, D'Amico, Mark, Lin, Bing, Watanabe, Genichi, ...
The neu (c-erbB-2) proto-oncogene encodes a tyrosine kinase receptor that is overexpressed in 20 to 30% of human breast tumors. Herein, cyclin D1 protein levels were increased in mammary tumors...
Dankort, David, Maslikowski, Bart, Warner, Neil, Kanno, Nubufumi, Kim, Harold, Wang, Zhixiang, ...
Amplification of the Neu (ErbB-2 or HER-2) receptor tyrosine kinase occurs in 20 to 30% of human mammary carcinomas, correlating with a poor clinical prognosis. We have previously demonstrated that...
Hutchinson, John, Jin, Jing, Cardiff, Robert D., Woodgett, Jim R., Muller, William J.
Activation of Akt by the phosphatidylinositol 3′-OH kinase (PI3K) results in the inhibition of proapoptotic signals and the promotion of survival signals (L. P. Kane et al., Curr. Biol....
Webster, Marc A., Hutchinson, John N., Rauh, Michael J., Muthuswamy, Senthil K., Anton, Martina, Tortorice, Christopher G., ...
Transgenic mice expressing the polyomavirus (PyV) middle T antigen (MT) develop multifocal mammary tumors which frequently metastasize to the lung. The potent transforming activity of PyV MT is...
Genetic instability favoring transversions associated with ErbB2-induced mammary tumorigenesis
Liu, Shiquan, Liu, Wenjing, Jakubczak, John L., Erexson, Gregory L., Tindall, Kenneth R., Chan, Richard, ...
It has been argued that genetic instability is required to generate the myriad mutations that fuel tumor initiation and progression and, in fact, patients with heritable cancer susceptibility...
Nguyen, AnhCo, Burack, W. Richard, Stock, Jeffrey L., Kortum, Robert, Chaika, Oleg V., Afkarian, Maryam, ...
While scaffold proteins are thought to be key components of signaling pathways, their exact function is unknown. By preassembling multiple components of signaling cascades, scaffolds are predicted to...
ErbB2 Is Required for Muscle Spindle and Myoblast Cell Survival
Andrechek, Eran R., Hardy, William R., Girgis-Gabardo, Adele A., Perry, Robert L. S., Butler, Richard, Graham, Frank L., ...
Signaling mediated by ErbB2 is thought to play a critical role in numerous developmental processes. However, due to the embryonic lethality associated with the germ line inactivation of erbB2, its...
The Catalytic Activity of the ErbB-2 Receptor Tyrosine Kinase Is Essential for Embryonic Development
Chan, Richard, Hardy, William R., Laing, Michael A., Hardy, Sarah E., Muller, William J.
Activation of the epidermal growth factor receptor (EGFR) family is thought to play a critical role in both embryogenesis and oncogenesis. The diverse biological activities of the EGFR family are...
Andrechek, Eran R, Muller, William J
The ability of growth factors and their cognate receptors to induce mammary epithelial proliferation and differentiation is dependent on their ability to activate a number of specific signal...
Williams, Terence M., Cheung, Michelle W.-C., Park, David S., Razani, Babak, Cohen, Alex W., Muller, William J., ...
Caveolin-1 is the principal structural component of caveolae microdomains, which represent a subcompartment of the plasma membrane. Several independent lines of evidence support the notion that...
Siegel, Peter M., Shu, Weiping, Cardiff, Robert D., Muller, William J., Massagué, Joan
The influence of transforming growth factor β (TGF-β) signaling on Neu-induced mammary tumorigenesis and metastasis was examined with transgenic mouse models. We generated mice expressing an...
De Candia, Paola, Solit, David B., Giri, Dilip, Brogi, Edi, Siegel, Peter M., Olshen, Adam B., ...
Id proteins bind basic helix–loop–helix transcription factors and function as dominant negative inhibitors of gene expression. Id1 and Id3 are required for the recruitment of bone marrow-derived...
Ets2-Dependent Stromal Regulation of Mouse Mammary Tumors
Man, Albert K., Young, Lawrence J. T., Tynan, John A., Lesperance, Jacqueline, Egeblad, Mikala, Werb, Zena, ...
The Ets2 transcription factor is regulated by mitogen-activated protein (MAP) kinase phosphorylation of a single threonine residue. We generated by gene targeting a single codon mutation in Ets2...
Saucier, Caroline, Khoury, Hanane, Lai, Ka-Man Venus, Peschard, Pascal, Dankort, David, Naujokas, Monica A., ...
The etiology and progression of a variety of human malignancies are linked to the deregulation of receptor tyrosine kinases (RTKs). To define the role of RTK-dependent signals in various oncogenic...
Andrechek, Eran R., Hardy, William R., Laing, Michael A., Muller, William J.
We have previously shown that mammary epithelial specific expression of the activated erbB2 allele under the control of the endogenous promoter in mice resulted in the formation of mammary...
HGF Converts ErbB2/Neu Epithelial Morphogenesis to Cell Invasion
Khoury, Hanane, Naujokas, Monica A., Zuo, Dongmei, Sangwan, Veena, Frigault, Melanie M., Petkiewicz, Stephanie, ...
Activation of the hepatocyte growth factor receptor Met induces a morphogenic response and stimulates the formation of branching tubules by Madin-Darby canine kidney (MDCK) epithelial cells in...
White, Donald E., Coutu, Pierre, Shi, Yan-Fen, Tardif, Jean-Claude, Nattel, Stanley, Arnaud, RenéSt., ...
A requirement for integrin-mediated adhesion in cardiac physiology is revealed through targeted deletion of inte-grin-associated genes in the murine heart. Here we show that targeted ablation of the...
Kupferman, Michael E., Fini, M. Elizabeth, Muller, William J., Weber, Randal, Cheng, Yi, Muschel, Ruth J.
Matrix metalloproteinase 9 (MMP-9, also known as gelatinase B or 92-kd Type IV collagenase) is overexpressed in many human and murine cancers. We induced carcinomas in mice carrying a transgene that...
Lin, Elaine Y., Jones, Joan G., Li, Ping, Zhu, Liyin, Whitney, Kathleen D., Muller, William J., ...
Animal models are powerful tools to analyze the mechanism of the induction of human breast cancer. Here we report a detailed analysis of mammary tumor progression in one mouse model of breast cancer...
Elevated Expression of DecR1 Impairs ErbB2/Neu-Induced Mammary Tumor Development▿ †
Ursini-Siegel, Josie, Rajput, Ashish B., Lu, Huiling, Sanguin-Gendreau, Virginie, Zuo, Dongmei, Papavasiliou, Vasilios, ...
Tumor cells utilize glucose as a primary energy source and require ongoing lipid biosynthesis for growth. Expression of DecR1, an auxiliary enzyme in the fatty acid β-oxidation pathway, is...
Dillon, Rachelle L., Brown, Stephen T., Ling, Chen, Shioda, Toshishiro, Muller, William J.
Amplification and elevated expression of the ErbB2 receptor tyrosine kinase occurs in 20% of human breast cancers and is associated with a poor prognosis. We have previously demonstrated that mammary...
Mammary epithelial-specific disruption of the focal adhesion kinase blocks mammary tumor progression
Lahlou, Hicham, Sanguin-Gendreau, Virginie, Zuo, Dongmei, Cardiff, Robert. D., McLean, Gordon W., Frame, Margaret C., ...
Elevated expression and activation of the focal adhesion kinase (FAK) occurs in a large proportion of human breast cancers. Although several studies have implicated FAK as an important signaling...
Northey, Jason J., Chmielecki, Juliann, Ngan, Elaine, Russo, Caterina, Annis, Matthew G., Muller, William J., ...
Cooperation between the Neu/ErbB-2 and transforming growth factor β (TGF-β) signaling pathways enhances the invasive and metastatic capabilities of breast cancer cells; however, the underlying...