Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes

Stewart, Timothy A.; Pattengale, Paul K.; Leder, Philip

doi:10.1016/0092-8674(84)90257-5

Cited by 847 publications

(456 citation statements)

References 41 publications

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“…Examination of MMTV-PTPe mRNA expression revealed that the transgene is expressed in the salivary glands and in the mammary glands of pregnant or lactating, but not virgin, transgenic mice, and is not expressed in mammary glands of a pregnant female mouse from a nonexpressing transgenic line (Figure 1c). This expression pattern is typical of the hormonally-regulated MMTV promoter (Stewart et al, 1984;Muller et al, 1988;Kitsberg and Leder, 1996;Krane and Leder, 1996). No expression of the transgene was observed in the lachrymatory Harderian gland, a site where MMTVbased transgenes are occasionally expressed (Sinn et al, 1987;Krane and Leder, 1996).…”

Section: Generation Of Mmtv-ptpe Transgenic Micementioning

confidence: 77%

Protein tyrosine phosphatase ε increases the risk of mammary hyperplasia and mammary tumors in transgenic mice

Elson

1999

Oncogene

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Accurate phosphorylation of tyrosine residues in proteins plays a central role in regulation of cellular function. Although connections between aberrant tyrosine kinase activity and malignancy are well-established, signi®cantly less is known about the roles of protein tyrosine phosphatases (PTPases) in tumorigenesis. We have previously shown that the transmembranal form of PTPase Epsilon (PTPe) is upregulated in mouse mammary tumors initiated speci®cally by ras or neu, suggesting that PTPe may play a role in transformation by these two oncogenes. In order to test this notion in vivo, we created transgenic mice that express elevated levels of PTPe in their mammary epithelium by use of the MMTV promoter/enhancer. Following several cycles of pregnancy female MMTV-PTPe mice uniformly developed pronounced and persistent mammary hyperplasia which was accompanied by residual milk production. Solitary mammary tumors were often detected secondary to mammary hyperplasia. The sporadic nature of the tumors, the long latency period prior to their development, and low levels of transgene expression in the tumors indicate that PTPe provides a necessary, but insu cient, signal for oncogenesis. The results provide genetic evidence that PTPe plays an accessory role in production of mammary tumors in a manner consistent with its upregulation in mammary tumors induced by ras or neu.

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Section: Generation Of Mmtv-ptpe Transgenic Micementioning

confidence: 77%

Protein tyrosine phosphatase ε increases the risk of mammary hyperplasia and mammary tumors in transgenic mice

Elson

1999

Oncogene

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“…In order to ascertain whether transgenic Bcl-2 expression had any cooperative e ect on tumorigenesis we crossed the WAP-bcl-2 transgenics with MMTVmyc transgenic mice. These mice develop mammary tumors spontaneously after a certain latency period due to transgenederived c-Myc expression in their mammary glands (Stewart et al, 1984). Double transgenic WAP-bcl-2/ MMTVmyc mice were compared to their single transgenic littermates.…”

Section: Inhibition Of Alveolar Cell Apoptosis During Involution By Bmentioning

confidence: 99%

Overexpression of Bcl-2 inhibits alveolar cell apoptosis during involution and accelerates c-myc-induced tumorigenesis of the mammary gland in transgenic mice

Jäger¹,

et al. 1997

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“…About half of the virgin female mice carrying the c-myc transgene under control of mouse mammary tumor virus (MMTV) long terminal repeat also develop spontaneous mammary carcinomas after 9 months of age (Stewart et al, 1984;Amundadottir et al, 1995Amundadottir et al, , 1996b. c-Myc-induced carcinogenesis may be further promoted by additional growth stimuli such as some female sex hormones, since multiple pregnancies markedly increase its incidence and shorten its latency period (Stewart et al, 1984;Amundadottir et al, 1995Amundadottir et al, , 1996b.…”

Section: Introductionmentioning

confidence: 99%

Cell cycle basis for the onset and progression of c-Myc-induced, TGFα-enhanced mouse mammary gland carcinogenesis

et al. 2000

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Using single and double transgenic mouse models, we investigated how c-Myc modulates the mammary epithelial cell cycle to induce cancer and how TGFa enhanced the process. In c-myc transgenic mice, c-myc expression was high in the hyperplastic mammary epithelium and in the majority of tumor areas. However, the tumors displayed focal areas of low expression of cmyc but high rates of proliferation. In contrast to E2F1 and cyclin A2, which were induced and co-localized with c-myc expression, induction of cyclins D1 and E occurred only in these tumor foci. Overexpression of cyclin D1 also occurred in the hyperplastic epithelium of tgfa-single and tgfa/c-myc-double transgenic mice. In tgfa/c-myc tumors, cells positive for cyclins D1 and E were randomly spread, without showing a reciprocal relationship to c-myc expression. In contrast to c-myc tumors, most tgfa/c-myc tumors showed undetectable levels of retinoblastoma protein (pRB), and the loss of pRB occurred in some cases at the mRNA level. These results suggest that E2F1 and cyclin A2 may be induced by c-Myc to mediate the onset of mammary cancer, whereas overexpression of cyclins D1 and E may occur later to facilitate tumor progression. TGFa may play its synergistic role, at least in part, by inducing cyclin D1 and facilitating the loss of pRB.

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Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes

Cited by 847 publications

References 41 publications

Protein tyrosine phosphatase ε increases the risk of mammary hyperplasia and mammary tumors in transgenic mice

Protein tyrosine phosphatase ε increases the risk of mammary hyperplasia and mammary tumors in transgenic mice

Overexpression of Bcl-2 inhibits alveolar cell apoptosis during involution and accelerates c-myc-induced tumorigenesis of the mammary gland in transgenic mice

Cell cycle basis for the onset and progression of c-Myc-induced, TGFα-enhanced mouse mammary gland carcinogenesis

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