Accelerated preclinical testing using transplanted tumors from genetically engineered mouse breast cancer models.

Accelerated preclinical testing using transplanted tumors from genetically engineered mouse breast cancer models. Research Abstract Details 

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Accelerated preclinical testing using transplanted tumors from genetically engineered mouse breast cancer models. Abstract Text:

Lyuba Varticovski,Melinda G Hollingshead,Ana I Robles,Xiaolin Wu,James Cherry,David J Munroe,Luanne Lukes,Miriam R Anver,John P Carter,Suzanne D Borgel,Howard Stotler,Carrie A Bonomi, Nunez,Stephen D Hursting,Wenhui Qiao,Chuxia X Deng,Jeff E Green,Kent W Hunter,Glenn Merlino,Patricia S Steeg,Lalage M Wakefield,J Carl Barrett,

PURPOSE: The use of genetically engineered mouse (GEM) models for preclinical testing of anticancer therapies is hampered by variable tumor latency, incomplete penetrance, and complicated breeding schemes. Here, we describe and validate a transplantation strategy that circumvents some of these difficulties. EXPERIMENTAL DESIGN: Tumor fragments from tumor-bearing MMTV-PyMT or cell suspensions from MMTV-PyMT, -Her2/neu, -wnt1, -wnt1/p53(+/-), BRCA1/p53(+/-), and C3(1)T-Ag mice were transplanted into the mammary fat pad or s.c. into naïve syngeneic or immunosuppressed mice. Tumor development was monitored and tissues were processed for histopathology and gene expression profiling. Metastasis was scored 60 days after the removal of transplanted tumors. RESULTS: PyMT tumor fragments and cell suspensions from anterior glands grew faster than posterior tumors in serial passages regardless of the site of implantation. Microarray analysis revealed genetic differences between these tumors. The transplantation was reproducible using anterior tumors from multiple GEM, and tumor growth rate correlated with the number of transplanted cells. Similar morphologic appearances were observed in original and transplanted tumors. Metastasis developed in >90% of mice transplanted with PyMT, 40% with BRCA1/p53(+/-) and wnt1/p53(+/-), and 15% with Her2/neu tumors. Expansion of PyMT and wnt1 tumors by serial transplantation for two passages did not lead to significant changes in gene expression. PyMT-transplanted tumors and anterior tumors of transgenic mice showed similar sensitivities to cyclophosphamide and paclitaxel. CONCLUSIONS: Transplantation of GEM tumors can provide a large cohort of mice bearing mammary tumors at the same stage of tumor development and with defined frequency of metastasis in a well-characterized molecular and genetic background.

Accelerated preclinical testing using transplanted tumors from genetically engineered mouse breast cancer models. Publishing Authors By Initials

L Varticovski,MG Hollingshead,AI Robles,X Wu,J Cherry,DJ Munroe,L Lukes,MR Anver,JP Carter,SD Borgel,H Stotler,CA Bonomi,NP Nunez,SD Hursting,W Qiao,CX Deng,JE Green,KW Hunter,G Merlino,PS Steeg,LM Wakefield,JC Barrett,

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Accelerated preclinical testing using transplanted tumors from genetically engineered mouse breast cancer models. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Clinical cancer research : an official journal of

VOLUME: 13

Page Numbers: 2168-77

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 1

MONTH: Apr

YEAR: 2007

Accelerated preclinical testing using transplanted tumors from genetically engineered mouse breast cancer models. Information

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LANGUAGE: eng

NlmUniqueID: 9502500

Accelerated preclinical testing using transplanted tumors from genetically engineered mouse breast cancer models. Keywords Mesh Terms:

KEYWORDS: Reverse Transcriptase Polymerase Chain R

MESH TERMS: methods

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Grant and Affiliation Information for Accelerated preclinical testing using transplanted tumors from genetically engineered mouse breast cancer models.

AFFILIATION: Center for Cancer Research, National Cancer Institute, Frederick, Maryland. varticol@mail.nih.gov

Country: United States

AGENCY: United States NCI

GRANT: N01-CO-12400

ACRONYM: CO

MEDLINETA: Clin Cancer Res

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