William C. Hahn

Structural Basis of PP2A Inhibition by Small t Antigen (2007)

Uhn Soo Cho, Seamus Morrone, Anna A. Sablina, Jason D. Arroyo, William C. Hahn, Wenqing Xu

The SV40 small t antigen (ST) is a potent oncoprotein that perturbs the function of protein phosphatase 2A (PP2A). ST directly interacts with the PP2A scaffolding A subunit and alters PP2A activity...

Minimizing the risk of reporting false positives in large-scale RNAi screens (2006)

Echeverri, Christophe J, Beachy, Philip A, Baum, Buzz, Boutros, Michael, Buchholz, Frank, Chanda, Sumit K, ...

Large-scale RNA interference (RNAi)-based analyses, very much as other 'omic' approaches, have inherent rates of false positives and negatives. The variability in the standards of care applied to...

Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants (2005)

Heidi Greulich, Tzu-Hsiu Chen, Whei Feng, Pasi A. Jänne, James V. Alvarez, Mauro Zappaterra, ...

Different EGFR mutations are associated with lung cancer. All of the classes can transform fibroblasts and lung epithelial cells, most are sensitive to erlotinib and gefininib, but exon 20 mutations...

Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants (2005)

Heidi Greulich, Tzu-Hsiu Chen, Whei Feng, Pasi A. Jänne, James V. Alvarez, Mauro Zappaterra, ...

Background Somatic mutations in the kinase domain of the epidermal growth factor receptor tyrosine kinase gene EGFR are common in lung adenocarcinoma. The presence of mutations correlates with tumor...

Development of Immortalized and Tumorigenic Prostate Cell Lines of Defined Genetic Constitution (1998)

Hahn, William C.

In order to develop a better understanding of the molecular events that transform normal human prostate cells into prostate cancer, we have developed a system of cell transformation that permits the...

Development of Immortalized and Tumorigenic Prostate Cell Lines of Defined Genetic Constitution (1998)

Hahn, William C.

In order to develop a better understanding of the molecular events that transform normal human prostate cells into prostate cancer, we have developed a system of cell transformation that permits the...

Development of Immortalized and Tumorigenic Prostate Cell Lines of Defined Genetic Constitution (1998)

Hahn, William C.

To develop an understanding of the molecular events that transform normal human prostate cells into prostate cancer, we have developed a system of cell transformation that permits the creation of...

Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization

Counter, Christopher M., Hahn, William C., Wei, Wenyi, Caddle, Stephanie Dickinson, Beijersbergen, Roderick L., Lansdorp, Peter M., ...

The immortalization of human cells is a critical step during tumorigenesis. In vitro, normal human somatic cells must overcome two proliferative blockades, senescence and crisis, to become immortal....

Human Keratinocytes That Express hTERT and Also Bypass a p16INK4a-Enforced Mechanism That Limits Life Span Become Immortal yet Retain Normal Growth and Differentiation Characteristics

Dickson, Mark A., Hahn, William C., Ino, Yasushi, Ronfard, Vincent, Wu, Jenny Y., Weinberg, Robert A., ...

Normal human cells exhibit a limited replicative life span in culture, eventually arresting growth by a process termed senescence. Progressive telomere shortening appears to trigger senescence in...

Telomerase contributes to tumorigenesis by a telomere length-independent mechanism

Stewart, Sheila A., Hahn, William C., O'Connor, Benjamin F., Banner, Elisa N., Lundberg, Ante S., Modha, Poonam, ...

Once immortalized, human cells are susceptible to transformation by introduction of an oncogene such as ras. Several lines of evidence now suggest that the maintenance of telomere length is a major...

Enumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell Transformation

Hahn, William C., Dessain, Scott K., Brooks, Mary W., King, Jessie E., Elenbaas, Brian, Sabatini, David M., ...

While it is clear that cancer arises from the accumulation of genetic mutations that endow the malignant cell with the properties of uncontrolled growth and proliferation, the precise combinations of...

A Two-Stage, p16INK4A- and p53-Dependent Keratinocyte Senescence Mechanism That Limits Replicative Potential Independent of Telomere Status†

Rheinwald, James G., Hahn, William C., Ramsey, Matthew R., Wu, Jenny Y., Guo, Zongyou, Tsao, Hensin, ...

With increasing frequency during serial passage in culture, primary human keratinocytes express p16INK4A (p16) and undergo senescence arrest. Keratinocytes engineered to express hTERT maintain long...

The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase

Johnson, F.Brad, Marciniak, Robert A., McVey, Mitch, Stewart, Sheila A., Hahn, William C., Guarente, Leonard

Werner syndrome (WS) is marked by early onset of features resembling aging, and is caused by loss of the RecQ family DNA helicase WRN. Precisely how loss of WRN leads to the phenotypes of WS is...

Abolition of Cyclin-Dependent Kinase Inhibitor p16Ink4a and p21Cip1/Waf1 Functions Permits Ras-Induced Anchorage-Independent Growth in Telomerase-Immortalized Human Fibroblasts

Wei, Wenyi, Jobling, Wendy A., Chen, Wen, Hahn, William C., Sedivy, John M.

Human cells are more resistant to both immortalization and malignant transformation than rodent cells. Recent studies have established the basic genetic requirements for the transformation of human...

Cyclin D1 overexpression and p53 inactivation immortalize primary oral keratinocytes by a telomerase-independent mechanism

Opitz, Oliver G., Suliman, Yasir, Hahn, William C., Harada, Hideki, Blum, Hubert E., Rustgi, Anil K.

The immortalization of human cells is a critical step in multistep carcinogenesis. Oral-esophageal carcinomas, a model system to investigate molecular mechanisms underlying squamous carcinogenesis,...

Expression of Telomerase RNA Template, but Not Telomerase Reverse Transcriptase, Is Limiting for Telomere Length Maintenance In Vivo

Chiang, Y. Jeffrey, Hemann, Michael T., Hathcock, Karen S., Tessarollo, Lino, Feigenbaum, Lionel, Hahn, William C., ...

Telomerase consists of two essential components, the telomerase RNA template (TR) and telomerase reverse transcriptase (TERT). The haplo-insufficiency of TR was recently shown to cause one form of...

The telomerase reverse transcriptase regulates chromatin state and DNA damage responses

Masutomi, Kenkichi, Possemato, Richard, Wong, Judy M. Y., Currier, Jennifer L., Tothova, Zuzana, Manola, Judith B., ...

Constitutive expression of telomerase prevents senescence and crisis by maintaining telomere homeostasis. However, recent evidence suggests that telomerase is dynamically regulated in normal cells...

Transformation of Human and Murine Fibroblasts without Viral Oncoproteins

Boehm, Jesse S., Hession, Meghan T., Bulmer, Sara E., Hahn, William C.

Murine embryo fibroblasts are readily transformed by the introduction of specific combinations of oncogenes; however, the expression of those same oncogenes in human cells fails to convert such cells...

Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants

Greulich, Heidi, Chen, Tzu-Hsiu, Feng, Whei, Jänne, Pasi A, Alvarez, James V, Zappaterra, Mauro, ...

Different EGFR mutations are associated with lung cancer. All of the classes can transform fibroblasts and lung epithelial cells, most are sensitive to erlotinib and gefininib, but exon 20 mutations...

Lentivirus-delivered stable gene silencing by RNAi in primary cells

STEWART, SHEILA A., DYKXHOORN, DEREK M., PALLISER, DEBORAH, MIZUNO, HANA, YU, EVAN Y., AN, DONG SUNG, ...

Genome-wide genetic approaches have proven useful for examining pathways of biological significance in model organisms such as Saccharomyces cerevisiae, Drosophila melanogastor, and Caenorhabditis...

Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells

Dolma, Sonam, Lessnick, Stephen L., Hahn, William C., Stockwell, Brent R.

We used synthetic lethal high-throughput screening to interrogate 23,550 compounds for their ability to kill engineered tumorigenic cells but not their isogenic normal cell counterparts. We...

Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells

Elenbaas, Brian, Spirio, Lisa, Koerner, Frederick, Fleming, Mark D., Zimonjic, Drazen B., Donaher, Joana Liu, ...

A number of genetic mutations have been identified in human breast cancers, yet the specific combinations of mutations required in concert to form breast carcinoma cells remain unknown. One approach...

Creating oral squamous cancer cells: A cellular model of oral–esophageal carcinogenesis

Goessel, Gitta, Quante, Michael, Hahn, William C., Harada, Hideki, Heeg, Steffen, Suliman, Yasir, ...

Immortalization and malignant transformation are important steps in tumor development. The ability to induce these processes from normal human epithelial cells with genetic alterations frequently...

Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization

Counter, Christopher M., Hahn, William C., Wei, Wenyi, Caddle, Stephanie Dickinson, Beijersbergen, Roderick L., Lansdorp, Peter M., ...

The immortalization of human cells is a critical step during tumorigenesis. In vitro, normal human somatic cells must overcome two proliferative blockades, senescence and crisis, to become immortal....

Human Keratinocytes That Express hTERT and Also Bypass a p16INK4a-Enforced Mechanism That Limits Life Span Become Immortal yet Retain Normal Growth and Differentiation Characteristics

Dickson, Mark A., Hahn, William C., Ino, Yasushi, Ronfard, Vincent, Wu, Jenny Y., Weinberg, Robert A., ...

Normal human cells exhibit a limited replicative life span in culture, eventually arresting growth by a process termed senescence. Progressive telomere shortening appears to trigger senescence in...

Telomerase contributes to tumorigenesis by a telomere length-independent mechanism

Stewart, Sheila A., Hahn, William C., O'Connor, Benjamin F., Banner, Elisa N., Lundberg, Ante S., Modha, Poonam, ...

Once immortalized, human cells are susceptible to transformation by introduction of an oncogene such as ras. Several lines of evidence now suggest that the maintenance of telomere length is a major...

Enumeration of the Simian Virus 40 Early Region Elements Necessary for Human Cell Transformation

Hahn, William C., Dessain, Scott K., Brooks, Mary W., King, Jessie E., Elenbaas, Brian, Sabatini, David M., ...

While it is clear that cancer arises from the accumulation of genetic mutations that endow the malignant cell with the properties of uncontrolled growth and proliferation, the precise combinations of...

A Two-Stage, p16INK4A- and p53-Dependent Keratinocyte Senescence Mechanism That Limits Replicative Potential Independent of Telomere Status†

Rheinwald, James G., Hahn, William C., Ramsey, Matthew R., Wu, Jenny Y., Guo, Zongyou, Tsao, Hensin, ...

With increasing frequency during serial passage in culture, primary human keratinocytes express p16INK4A (p16) and undergo senescence arrest. Keratinocytes engineered to express hTERT maintain long...

The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase

Johnson, F.Brad, Marciniak, Robert A., McVey, Mitch, Stewart, Sheila A., Hahn, William C., Guarente, Leonard

Werner syndrome (WS) is marked by early onset of features resembling aging, and is caused by loss of the RecQ family DNA helicase WRN. Precisely how loss of WRN leads to the phenotypes of WS is...

Abolition of Cyclin-Dependent Kinase Inhibitor p16Ink4a and p21Cip1/Waf1 Functions Permits Ras-Induced Anchorage-Independent Growth in Telomerase-Immortalized Human Fibroblasts

Wei, Wenyi, Jobling, Wendy A., Chen, Wen, Hahn, William C., Sedivy, John M.

Human cells are more resistant to both immortalization and malignant transformation than rodent cells. Recent studies have established the basic genetic requirements for the transformation of human...

Cyclin D1 overexpression and p53 inactivation immortalize primary oral keratinocytes by a telomerase-independent mechanism

Opitz, Oliver G., Suliman, Yasir, Hahn, William C., Harada, Hideki, Blum, Hubert E., Rustgi, Anil K.

The immortalization of human cells is a critical step in multistep carcinogenesis. Oral-esophageal carcinomas, a model system to investigate molecular mechanisms underlying squamous carcinogenesis,...

Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells

Elenbaas, Brian, Spirio, Lisa, Koerner, Frederick, Fleming, Mark D., Zimonjic, Drazen B., Donaher, Joana Liu, ...

A number of genetic mutations have been identified in human breast cancers, yet the specific combinations of mutations required in concert to form breast carcinoma cells remain unknown. One approach...

Expression of Telomerase RNA Template, but Not Telomerase Reverse Transcriptase, Is Limiting for Telomere Length Maintenance In Vivo

Chiang, Y. Jeffrey, Hemann, Michael T., Hathcock, Karen S., Tessarollo, Lino, Feigenbaum, Lionel, Hahn, William C., ...

Telomerase consists of two essential components, the telomerase RNA template (TR) and telomerase reverse transcriptase (TERT). The haplo-insufficiency of TR was recently shown to cause one form of...

The telomerase reverse transcriptase regulates chromatin state and DNA damage responses

Masutomi, Kenkichi, Possemato, Richard, Wong, Judy M. Y., Currier, Jennifer L., Tothova, Zuzana, Manola, Judith B., ...

Constitutive expression of telomerase prevents senescence and crisis by maintaining telomere homeostasis. However, recent evidence suggests that telomerase is dynamically regulated in normal cells...

Transformation of Human and Murine Fibroblasts without Viral Oncoproteins

Boehm, Jesse S., Hession, Meghan T., Bulmer, Sara E., Hahn, William C.

Murine embryo fibroblasts are readily transformed by the introduction of specific combinations of oncogenes; however, the expression of those same oncogenes in human cells fails to convert such cells...

Oncogenic Transformation by Inhibitor-Sensitive and -Resistant EGFR Mutants

Greulich, Heidi, Chen, Tzu-Hsiu, Feng, Whei, Jänne, Pasi A, Alvarez, James V, Zappaterra, Mauro, ...

Different EGFR mutations are associated with lung cancer. All of the classes can transform fibroblasts and lung epithelial cells, most are sensitive to erlotinib and gefininib, but exon 20 mutations...

Creating oral squamous cancer cells: A cellular model of oral–esophageal carcinogenesis

Goessel, Gitta, Quante, Michael, Hahn, William C., Harada, Hideki, Heeg, Steffen, Suliman, Yasir, ...

Immortalization and malignant transformation are important steps in tumor development. The ability to induce these processes from normal human epithelial cells with genetic alterations frequently...

Lentivirus-delivered stable gene silencing by RNAi in primary cells

STEWART, SHEILA A., DYKXHOORN, DEREK M., PALLISER, DEBORAH, MIZUNO, HANA, YU, EVAN Y., AN, DONG SUNG, ...

Genome-wide genetic approaches have proven useful for examining pathways of biological significance in model organisms such as Saccharomyces cerevisiae, Drosophila melanogastor, and Caenorhabditis...

Structural Basis of PP2A Inhibition by Small t Antigen

Cho, Uhn Soo, Morrone, Seamus, Sablina, Anna A, Arroyo, Jason D, Hahn, William C, Xu, Wenqing

The SV40 small t antigen (ST) is a potent oncoprotein that perturbs the function of protein phosphatase 2A (PP2A). ST directly interacts with the PP2A scaffolding A subunit and alters PP2A activity...

The SIRT1 Deacetylase Suppresses Intestinal Tumorigenesis and Colon Cancer Growth

Firestein, Ron, Blander, Gil, Michan, Shaday, Oberdoerffer, Philipp, Ogino, Shuji, Campbell, Jennifer, ...

Numerous longevity genes have been discovered in model organisms and altering their function results in prolonged lifespan. In mammals, some have speculated that any health benefits derived from...

Feedback Circuit among INK4 Tumor Suppressors Constrains Human Glioblastoma Development

Wiedemeyer, Ruprecht, Brennan, Cameron, Heffernan, Timothy P., Xiao, Yonghong, Mahoney, John, Protopopov, Alexei, ...

We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18INK4C and p16INK4A...