Dataset Information

Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.

ABSTRACT: Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors.Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, TgMMTV-PyMT, TgWAP-Int3, TgWAP-Tag, and TgC3(1)-Tag) yielded tumors with distinctive and homogeneous expression patterns within each strain. However, in each of four other models (TgWAP-T121, TgMMTV-Wnt1, Brca1Co/Co;TgMMTV-Cre;p53+/- and DMBA-induced), tumors with a variety of histologies and expression profiles developed. In many models, similarities to human breast tumors were recognized, including proliferation and human breast tumor subtype signatures. Significantly, tumors of several models displayed characteristics of human basal-like breast tumors, including two models with induced Brca1 deficiencies. Tumors of other murine models shared features and trended towards significance of gene enrichment with human luminal tumors; however, these murine tumors lacked expression of estrogen receptor (ER) and ER-regulated genes. TgMMTV-Neu tumors did not have a significant gene overlap with the human HER2+/ER- subtype and were more similar to human luminal tumors.Many of the defining characteristics of human subtypes were conserved among the mouse models. Although no single mouse model recapitulated all the expression features of a given human subtype, these shared expression features provide a common framework for an improved integration of murine mammary tumor models with human breast tumors.

SUBMITTER: Herschkowitz JI

PROVIDER: S-EPMC1929138 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.

Herschkowitz Jason I JI Simin Karl K Weigman Victor J VJ Mikaelian Igor I Usary Jerry J Hu Zhiyuan Z Rasmussen Karen E KE Jones Laundette P LP Assefnia Shahin S Chandrasekharan Subhashini S Backlund Michael G MG Yin Yuzhi Y Khramtsov Andrey I AI Bastein Roy R Quackenbush John J Glazer Robert I RI Brown Powel H PH Green Jeffrey E JE Kopelovich Levy L Furth Priscilla A PA Palazzo Juan P JP Olopade Olufunmilayo I OI Bernard Philip S PS Churchill Gary A GA Van Dyke Terry T Perou Charles M CM

Genome biology 20070101 5

<h4>Background</h4>Although numerous mouse models of breast carcinomas have been developed, we do not know the extent to which any faithfully represent clinically significant human phenotypes. To address this need, we characterized mammary tumor gene expression profiles from 13 different murine models using DNA microarrays and compared the resulting data to those from human breast tumors.<h4>Results</h4>Unsupervised hierarchical clustering analysis showed that six models (TgWAP-Myc, TgMMTV-Neu, ...[more]

PMID: 17493263

Similar Datasets

Project description:Novel synthetic compounds, known as manganese porphyrins (MnPs), have been designed to shift the redox status of both normal cells and cancer cells. When MnPs are coupled with cancer therapies, such as radiation, they have been shown to sensitize tumor cells to treatment and protect normal tissues from damage through the modulation of the redox status of various tissue types. Until now, our preclinical studies have focused on local effects of MnPs and radiation; however, we recognize that successful outcomes for cancer patients involve control of tumor cells throughout the body. In this study, using murine orthotopic mammary tumor models, we investigated how MnPs and radiation influence the development of distant metastasis. We hypothesized that the combination of MnP (MnP/RT), such as MnTnBuOE-2-PyP5+ and radiation treatment (RT) would increase local tumor control via a shift in the intratumoral redox environment, leading to subsequent downregulation of HIF-1 in the primary tumor. Secondarily, we hypothesized that these primary tumor treatment effects would result in a reduction in pulmonary metastatic burden. Balb/c mice with orthotopic 4T1 mammary carcinomas were treated with saline, MnP, RT or MnP/RT. We found MnP/RT did extend local tumor growth delay and overall survival compared to controls and was associated with increased intratumoral oxidative stress. However, the primary tumor growth delay observed with MnP/RT was not associated with a reduced pulmonary metastatic burden. Future directions to investigate the effects of MnP/RT on the development of distant metastasis may include modifications to the radiation dose, the experimental timeline or using a murine mammary carcinoma cell line with a less aggressive metastatic behavior. Clinical trials are underway to investigate the clinical utility of MnTnBuOE-2-PyP5+ for patients undergoing radiotherapy for various tumor types. The promising preclinical data from this study, as well as others, provides support that MnP/RT has the potential to improve local tumor control for these patients.

Dataset Information

Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.

Publications

Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets