Early and multifocal tumors in breast, salivary, Harderian and epididymal tissues developed in MMTY-Neu transgenic mice

Lucchini, Franco; Sacco, Maria Grazia; Hu, Nanpin; Villa, Anna; Brown, John P.; Cesano, L; Mangiarini, Laura; Rindi, Guido; Kindl, S.; Sessa, Fausto; Vezzoni, Paolo; Clerici, Libero

doi:10.1016/0304-3835(92)90044-v

Cited by 114 publications

(108 citation statements)

References 13 publications

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“…To ascertain whether HER2/Neu tumors are dependent on PI3K for maintaining tumor cells in their transformed state, we crossed floxed p110 mice with another HER2/Neu mammary tumor model, MMTV-NeuT (Lucchini et al 1992). Established NeuT-driven tumors carrying floxed p110 alleles were isolated, and dissociated tumor cells were treated with AdCre to delete p110.…”

Section: The P110a Isoform Is Required For the Growth Of Established mentioning

confidence: 99%

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The p110α and p110β isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis

Utermark¹,

Rao²,

Cheng³

et al. 2012

Genes Dev.

121

115

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Class Ia phosphatidylinositol 3 kinase (PI3K) is required for oncogenic receptor-mediated transformation; however, the individual roles of the two commonly expressed class Ia PI3K isoforms in oncogenic receptor signaling have not been elucidated in vivo. Here, we show that genetic ablation of p110a blocks tumor formation in both polyoma middle T antigen (MT) and HER2/Neu transgenic models of breast cancer. Surprisingly, p110b ablation results in both increased ductal branching and tumorigenesis. Biochemical analyses suggest a competition model in which the less active p110b competes with the more active p110a for receptor binding sites, thereby modulating the level of PI3K activity associated with activated receptors. Our findings demonstrate a novel p110b-based regulatory role in receptor-mediated PI3K activity and identify p110a as an important target for treatment of HER2-positive disease.

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Section: The P110a Isoform Is Required For the Growth Of Established mentioning

confidence: 99%

“…MMTV-MT (Guy et al 1992) and NIC (Ursini- Siegel et al 2008) were in the FVB/N background. MMTV-NeuT mice were in the Balb/c background (Lucchini et al 1992). NCrNu female mice (Taconic) were used for orthotopic transplantation.…”

Section: Animalsmentioning

confidence: 99%

The p110α and p110β isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis

Utermark¹,

Rao²,

Cheng³

et al. 2012

Genes Dev.

121

115

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“…To directly test the importance of erbB-2 in mammary tumorigenesis, transgenic mice carrying an activated form of the erbB-2/neu oncogene under the transcriptional control of the mouse mammary tumor virus long terminal repeat were derived. Mammary epithelial speci®c-expression of a constitutively active ErbB-2 or a similarly altered human erbB-2 in the mammary epithelium of transgenic mice (Bouchard et al, 1989;Guy et al, 1996;Luchini et al, 1992;Muller et al, 1988;Stocklin et al, 1993) results in the rapid induction of mammary tumors that histologically resemble human comedocarcinomas (Cardi and Muller, 1993). Interestingly, human comedo-carcinomas express elevated ErbB-2 levels (Morrison, 1994), have a higher proliferative rate and are clinically more severe than other ductal carcinoma in situ (Patchefsky et al, 1989).…”

Section: Erbb-2 Plays a Causal Role In Mammary Tumorigenesismentioning

confidence: 99%

Signal transduction in mammary tumorigenesis: a transgenic perspective

Dankort

Muller

2000

Oncogene

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“…Inbred BALB/c mice engineered to overexpress the activated (G664E) neu oncogene under the control of the mouse mammary tumor virus promoter (MMTV-LTR; referred to as neuT mice) were used as experimental model system. 44 The transgene is prevalently expressed in mammary glands in these mice. At 3 weeks of age, female neuT mice start a process of rapid development of tumors involving all the mammary glands.…”

Section: Ad Mediated Immunization In Spontaneous Mouse Tumor Modelsmentioning

confidence: 99%

Adenovirus as vehicle for anticancer genetic immunotherapy

et al. 2005

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Adenoviruses (Ads) are in the forefront of genetic immunization methods being developed against cancer. Their ability to elicit an effective immune response against tumorassociated antigens has been demonstrated in many model systems. Several clinical trials, which use Ad as vehicle for immunization, are already in progress. Preclinical studies have also demonstrated the efficacy of combining Ad-mediated immunization with adjuvants such as chemotherapeutic agents and cytokines. Issues related to sero-prevalence and safety of Ads, however, continue to pose a challenge and need to be addressed. Gene Therapy (2005) 12, S84-S91.

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Early and multifocal tumors in breast, salivary, Harderian and epididymal tissues developed in MMTY-Neu transgenic mice

Cited by 114 publications

References 13 publications

The p110α and p110β isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis

The p110α and p110β isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis

Signal transduction in mammary tumorigenesis: a transgenic perspective

Adenovirus as vehicle for anticancer genetic immunotherapy

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