Reference SummaryBerton TR, Oncogene 2003 Aug 21;22(35):5415-26

Title

 Tumor formation in mice with conditional inactivation of Brca1 in epithelial tissues.

Authors

 Berton TR; Matsumoto T; Page A; Conti CJ; Deng CX; Jorcano JL; Johnson DG

Journal

 Oncogene

Volume

 22

Issue

 35

Year

 2003

Pages

 5415-26

Abstract

 The BRCA1 tumor-suppressor protein has been implicated in the regulation of transcription, DNA repair, proliferation, and apoptosis. BRCA1 is expressed in many proliferative tissues and this is at least in part due to E2F-dependent transcriptional control. In this study, inactivation of a conditional murine Brca1 allele was achieved in a variety of epithelial tissues via expression of the Cre recombinase under the control of a keratin 5 (K5) promoter. The K5 Cre:Brca1 conditional knockout mice exhibited modest epidermal hyperproliferation, increased apoptosis, and were predisposed to developing tumors in the skin, the inner ear canal, and the oral epithelium after 1 year of age. Overexpression of the E2F1 transcription factor in K5 Cre:Brca1 conditional knockout mice dramatically accelerated tumor development. In addition, Brca1 heterozygous female mice that had elevated E2F1 expression developed tumors of the reproductive tract at high incidence. These findings demonstrate that in mice Brca1 functions as a tumor suppressor in other epithelial tissues in addition to the mammary gland. Moreover, inactivation of Brca1 is shown to cooperate with deregulation of the Rb-E2F1 pathway to promote tumorigenesis.

Links

 J:85354 – MGI References
12934101 – National Library of Medicine/PubMed

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Ear - Inner ear carcinoma - basal Ear - Inner ear

5.56
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Ear squamous cell carcinoma Ear

16.67
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Tg(KRT5-E2F1)2Dgj Ear tumor Ear

0
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Ear tumor - epithelial Ear

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Ear tumor - epithelial Ear

0
[not specified]-Brca1tm2Cxd/+ Ear tumor - epithelial Ear

0
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-E2F1)2Dgj Ear tumor - epithelial Ear

observed
[not specified]-Brca1tm2Cxd/+ Tg(KRT5-E2F1)2Dgj Ear tumor - epithelial Ear

0
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Leukocyte lymphoma Leukocyte

5.56
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Mesodermal cell/mesoblast sarcoma Gastrointestinal tract

5.56
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Mesodermal cell/mesoblast sarcoma - undifferentiated Mesodermal cell/mesoblast

5.56
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Mouth squamous cell carcinoma Mouth

3.33
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Tg(KRT5-E2F1)2Dgj Mouth squamous cell carcinoma Mouth

20
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Tg(KRT5-E2F1)2Dgj Mouth tumor Mouth

20
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Mouth tumor - epithelial Mouth

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Mouth tumor - epithelial Mouth

0
[not specified]-Brca1tm2Cxd/+ Mouth tumor - epithelial Mouth

0
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-E2F1)2Dgj Mouth tumor - epithelial Mouth

observed
[not specified]-Brca1tm2Cxd/+ Tg(KRT5-E2F1)2Dgj Mouth tumor - epithelial Mouth

16.67
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Skin squamous cell carcinoma Skin

22.22
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Tg(KRT5-E2F1)2Dgj Skin squamous cell carcinoma Skin

100
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-E2F1)2Dgj Skin squamous cell carcinoma Skin

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Skin tumor - epithelial Skin

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Skin tumor - epithelial Skin

0
[not specified]-Brca1tm2Cxd/+ Skin tumor - epithelial Skin

0
[not specified]-Brca1tm2Cxd/+ Tg(KRT5-E2F1)2Dgj Skin tumor - epithelial Skin

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Stomach squamous cell carcinoma Stomach

4.76
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-E2F1)2Dgj Uterus - Cervix papilloma Uterus - Cervix

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-E2F1)2Dgj Uterus - Cervix squamous cell carcinoma Uterus - Cervix

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Tg(KRT5-E2F1)2Dgj Uterus - Cervix tumor Uterus - Cervix

0
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Uterus - Cervix tumor - epithelial Uterus - Cervix

0
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Uterus - Cervix tumor - epithelial Uterus - Cervix

0
[not specified]-Brca1tm2Cxd/+ Uterus - Cervix tumor - epithelial Uterus - Cervix

0
[not specified]-Brca1tm2Cxd/+ Tg(KRT5-E2F1)2Dgj Uterus - Cervix tumor - epithelial Uterus - Cervix

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Vagina squamous cell carcinoma Vagina

5.56
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-E2F1)2Dgj Vagina squamous cell carcinoma Vagina

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Tg(KRT5-E2F1)2Dgj Vagina tumor Vagina

0
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj Vagina tumor - epithelial Vagina

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Vagina tumor - epithelial Vagina

0
[not specified]-Brca1tm2Cxd/+ Vagina tumor - epithelial Vagina

0
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-E2F1)2Dgj Vagina tumor - epithelial Vagina

observed
[not specified]-Brca1tm2Cxd/+ Tg(KRT5-E2F1)2Dgj Vagina tumor - epithelial Vagina

observed
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj (Unspecified organ) tumor (Unspecified organ)

72.22
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd (Unspecified organ) tumor (Unspecified organ)

4.76
[not specified]-Brca1tm2Cxd/+ Tg(KRT5-cre)5132Jlj (Unspecified organ) tumor (Unspecified organ)

0
[not specified]-Brca1tm2Cxd/+ (Unspecified organ) tumor (Unspecified organ)

5.88
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-E2F1)2Dgj (Unspecified organ) tumor (Unspecified organ)

94.74
[not specified]-Brca1tm2Cxd/+ Tg(KRT5-E2F1)2Dgj (Unspecified organ) tumor (Unspecified organ)

50
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-cre)5132Jlj (Unspecified organ) tumor - epithelial (Unspecified organ)

42.86
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd (Unspecified organ) tumor - epithelial (Unspecified organ)

0
[not specified]-Brca1tm2Cxd/+ (Unspecified organ) tumor - epithelial (Unspecified organ)

0
[not specified]-Brca1tm1Cxd/Brca1tm2Cxd Tg(KRT5-E2F1)2Dgj (Unspecified organ) tumor - epithelial (Unspecified organ)

94.74