Linked Life Data

15520179

Source:http://linkedlifedata.com/resource/pubmed/id/15520179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2004-11-2
pubmed:abstractText
Genetically engineered mouse mammary cancer models have been used over the years as systems to study human breast cancer. However, much controversy exists on the utility of such models as valid equivalents to the human cancer condition. To perform an interspecies gene expression comparative study in breast cancer we used a mouse model that most closely resembles human breast carcinogenesis. This system relies on the transplant of p53 null mouse mammary epithelial cells into the cleared mammary fat pads of syngeneic hosts. Serial analysis of gene expression (SAGE) was used to obtain gene expression profiles of normal and tumor samples from this mouse mammary cancer model (>300,000 mouse mammary-specific tags). The resulting mouse data were compared with 25 of our human breast cancer SAGE libraries (>2.5 million human breast-specific tags). We observed significant similarities in the deregulation of specific genes and gene families when comparing mouse with human breast cancer SAGE data. A total of 72 transcripts were identified as commonly deregulated in both species. We observed a systematic and significant down-regulation in all of the tumors from both species of various cytokines, including CXCL1 (GRO1), LIF, interleukin 6, and CCL2. All of the mouse and most human mammary tumors also displayed decreased expression of genes known to inhibit cell proliferation, including NFKBIA (IKBalpha), GADD45B, and CDKN1A (p21); transcription-related genes such as CEBP, JUN, JUNB, and ELF1; and apoptosis-related transcripts such as IER3 and GADD34/PPP1R15A. Examples of overexpressed transcripts in tumors from both species include proliferation-related genes such as CCND1, CKS1B, and STMN1 (oncoprotein 18); and genes related to other functions such as SEPW1, SDFR1, DNCI2, and SP110. Importantly, abnormal expression of several of these genes has not been associated previously with breast cancer. The consistency of these observations was validated in independent mouse and human mammary cancer sets. This is the first interspecies comparison of mammary cancer gene expression profiles. The comparative analysis of mouse and human SAGE mammary cancer data validates this p53 null mouse tumor model as a useful system closely resembling human breast cancer development and progression. More importantly, these studies are allowing us to identify relevant biomarkers of potential use in human studies while leading to a better understanding of specific mechanisms of human breast carcinogenesis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CCL2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CXCL1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CCL2, http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL1, http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC, http://linkedlifedata.com/resource/pubmed/chemical/Cytokines, http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6, http://linkedlifedata.com/resource/pubmed/chemical/LIF protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Leukemia Inhibitory Factor, http://linkedlifedata.com/resource/pubmed/chemical/Lif protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Proteins
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7748-55
pubmed:dateRevised
2011-4-12
pubmed:meshHeading
pubmed-meshheading:15520179-Animals, pubmed-meshheading:15520179-Apoptosis, pubmed-meshheading:15520179-Breast Neoplasms, pubmed-meshheading:15520179-Cell Division, pubmed-meshheading:15520179-Chemokine CCL2, pubmed-meshheading:15520179-Chemokine CXCL1, pubmed-meshheading:15520179-Chemokines, CXC, pubmed-meshheading:15520179-Cytokines, pubmed-meshheading:15520179-Female, pubmed-meshheading:15520179-Gene Expression Profiling, pubmed-meshheading:15520179-Gene Expression Regulation, Neoplastic, pubmed-meshheading:15520179-Humans, pubmed-meshheading:15520179-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:15520179-Interleukin-6, pubmed-meshheading:15520179-Leukemia Inhibitory Factor, pubmed-meshheading:15520179-Mammary Neoplasms, Experimental, pubmed-meshheading:15520179-Mice, pubmed-meshheading:15520179-NF-kappa B, pubmed-meshheading:15520179-Proteins
pubmed:year
2004
pubmed:articleTitle
From mice to humans: identification of commonly deregulated genes in mammary cancer via comparative SAGE studies.
pubmed:affiliation
Department of Carcinogenesis, The University of Texas M.D. Anderson Cancer Center, Science Park-Research Division, Smithville 78957, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't