Reference SummaryDeeb KK, Cancer Res 2007 Sep 1;67(17):8065-8080

Title

Identification of an Integrated SV40 T/t-Antigen Cancer Signature in Aggressive Human Breast, Prostate, and Lung Carcinomas with Poor Prognosis.

Authors

Deeb KK; Michalowska AM; Yoon CY; Krummey SM; Hoenerhoff MJ; Kavanaugh C; Li MC; Demayo FJ; Linnoila I; Deng CX; Lee EY; Medina D; Shih JH; Green JE

Journal

Cancer Res

Volume

67

Issue

17

Year

2007

Pages

8065-8080

Abstract

Understanding the genetic architecture of cancer pathways that distinguishes subsets of human cancer is critical to developing new therapies that better target tumors based on their molecular expression profiles. In this study, we identify an integrated gene signature from multiple transgenic models of epithelial cancers intrinsic to the functions of the Simian virus 40 T/t-antigens that is associated with the biological behavior and prognosis for several human epithelial tumors. This genetic signature, composed primarily of genes regulating cell replication, proliferation, DNA repair, and apoptosis, is not a general cancer signature. Rather, it is uniquely activated primarily in tumors with aberrant p53, Rb, or BRCA1 expression but not in tumors initiated through the overexpression of myc, ras, her2/neu, or polyoma middle T oncogenes. Importantly, human breast, lung, and prostate tumors expressing this set of genes represent subsets of tumors with the most aggressive phenotype and with poor prognosis. The T/t-antigen signature is highly predictive of human breast cancer prognosis. Because this class of epithelial tumors is generally intractable to currently existing standard therapies, this genetic signature identifies potential targets for novel therapies directed against these lethal forms of cancer. Because these genetic targets have been discovered using mammary, prostate, and lung T/t-antigen mouse cancer models, these models are rationale candidates for use in preclinical testing of therapies focused on these biologically important targets. [Cancer Res 2007;67(17):8065-80].

Links

17804718 – National Library of Medicine/PubMed

Strain Notes

Strain Note
C57BL/6-Tg(TRAMP)8247Ng/J These mice were purchased from The Jackson Laboratory.
FVB.Cg-Tg(MMTV-Erbb2)#Pjo These mice were described as being on an FVB background.
FVB.Cg-Tg(MMTV-vHaras)#Pjo These mice were described as being on an FVB background.

Models

Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
FVB Lung normal tissue (control) Lung

not applicable

FVB-Tg(Utg-TAg)#Fjd Lung tumor Lung

observed

FVB Mammary gland normal tissue (control) Mammary gland

not applicable

FVB-Tg(C3-1-TAg)cJeg Mammary gland tumor Mammary gland

observed

B6;129-Tg(Wap-rtTA-cre)10Whl Trp53tm1Elee Mammary gland tumor Mammary gland

observed

STOCK Brca1tm2Cxd Tg(MMTV-cre)4Mam Trp53tm1Brd Mammary gland tumor Mammary gland

observed

FVB.Cg-Tg(MMTV-Erbb2)#Pjo Mammary gland tumor Mammary gland

observed

FVB.Cg-Tg(MMTV-vHaras)#Pjo Mammary gland tumor Mammary gland

observed

FVB.Cg-Tg(MMTV-Myc)147-9bLed Mammary gland tumor Mammary gland

observed

FVB-Tg(MMTV-PyVT)634Mul Mammary gland tumor Mammary gland

observed

C57BL/6 Prostate gland normal tissue (control) Prostate gland

not applicable

C57BL/6-Tg(TRAMP)8247Ng/J Prostate gland tumor Prostate gland

observed

C57BL/6 Seminal vesicle normal tissue (control) Seminal vesicle

not applicable

C57BL/6-Tg(TRAMP)8247Ng/J Seminal vesicle tumor - phyllodes Seminal vesicle

observed