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Table 2 Validation of pathway predictions

From: A genomic analysis of mouse models of breast cancer reveals molecular features ofmouse models and relationships to human breast cancer

Model

Pathway

Effect

References

APC cKO

B-Catenin

Demonstrated high activation of β-catenin signaling in thesetumors.

[65]

APC cKO

Myc

High levels of Myc demonstrated by IHC in these mammary tumors.

[65]

BRCA & P53 mut

EGFR

Using IHC, EGFR was shown to be overexpressed in this mouse model.

[68]

DMBA

Ras

Observation of H-Ras mutations in mammary hyperplastic outgrowthsafter treatment with DMBA.

[69]

DMBA

EGFR

Using western blot and IHC, EGFR signaling was shown to be active inDMBA induced mammary tumors.

[70]

ETV6-Ntrk3

Src

ETV6-Ntrk3 binds to and activates c-Src, and inhibition of c-Srcactivation blocks EN transforming activity using mouse engineeredmouse embryonic fibroblasts.

[71]

Myc

Ras

Activating mutations in K-Ras found in a subset MMTV-Myc inducedtumors with a predicted elevation of Ras signalling.

[15]

Myc

B-Catenin

IHC analysis demonstrates higher expression of B-Catenin in themicroacinar histology of Myc driven tumors.

[15]

Myc

E2F1 E2F2 E2F3

E2F loss altered tumor latency and Myc proliferative effects on themammary gland.

[20]

Neu

Akt

Akt loss effects tumor development in the MMTV-Neu mouse model.

[72]

Neu

B-Catenin

Using a beta-gal reporter, ß-catenin/TCF-dependent transcriptionwas shown to be elevated in MMTV-Neu mouse mammary glands.

[73]

Notch

B-Catenin

Knocking down Notch in a human breast cancer cell line also impactedlevels of beta-catenin.

[74]

PyMT

Tgfb

Blockade of TGF-beta inhibits mammary tumor metastasis.

[75]

PyMT

Src

Loss of c-Src greatly reduced the occurrence of mammary tumors in theMMTV-PyMT mouse model.

[76]

Tag

Ras

K-ras amplifications observed in large t-antigen mediatedtumorigeneis.

[77]

Tag

E2F2 E2F3 RB KO

Large T Antigen simulates loss of Rb by leading to deregulatedacitvation of the E2F transcription factors.

[78]

Wnt

p53

MMTV-Wnt1 mammary tumors with mutant p53 exhibited a superior clinicalresponse compared to tumors with wild-type p53.

[79]

  1. DMBA, 7,12-dimethylbenz[a]anthracene; EGFR, epidermal growth factorreceptor; IHC, immunohistochemistry; MMTV, mouse mammary tumor virus; PyMT,polyoma middle T; TGF, transforming growth factor.