Reference SummaryAmundadottir LT, Cell Growth Differ 1995 Jun;6(6):737-48
Title |
Synergistic interaction of transforming growth factor alpha and c-myc in mouse mammary and salivary gland tumorigenesis. | ||||||||||||
Authors |
Amundadottir LT; Johnson MD; Merlino G; Smith GH; Dickson RB | ||||||||||||
Journal |
Cell Growth Differ | ||||||||||||
Volume |
6 | ||||||||||||
Issue |
6 | ||||||||||||
Year |
1995 | ||||||||||||
Pages |
737-48 | ||||||||||||
Abstract |
The c-myc oncogene is commonly amplified in breast cancer and is known to interact synergistically with transforming growth factor alpha (TGF alpha) in vitro to promote phenotypic transformation of mammary epithelial cells. In addition, both genes are under sex steroid hormone regulation in breast cancer. We have used a bitransgenic mouse approach to test the relevance of Myc-TGF alpha interaction in mammary gland tumorigenesis of virgin animals in vivo. We mated single transgenic TGF alpha and c-myc mouse strains to yield double transgenic offspring for TGF alpha and c-myc. All (20 of 20) double transgenic TGF alpha/c-myc animals developed synchronous mammary tumors at a mean age of 66 days. An unexpected finding was that tumor latency and frequency in males and virgin females were identical. Thus, two gene products that are known to be coinduced in breast cancer by the sex hormones estrogen and progesterone strongly synergize to induce synchronous mammary tumors, independent of sex. The tumors, despite being estrogen receptor positive, were readily transplanted as highly malignant s.c. cancers in ovariectomized nude mice. Although approximately one-half of single transgenic c-myc virgin females also eventually developed mammary gland tumors, these were stochastic and arose after a long latency period of 9-12 months. Single transgenic virgin TGF alpha females and males, c-myc males, and transgene-negative littermates did not develop tumors (ages up to 15 months). The salivary glands of double transgenic animals also coexpress the two transgenes and show pathological abnormalities ranging from hyperplasias to frank adenocarcinomas. In contrast, the salivary glands of single transgenic and wild-type animals showed only mild hyperplasias or metaplasias, but tumors were not observed. In situ hybridization analysis of mammary and salivary glands revealed that hyperplastic and tumorous areas colocalize with regions that overexpress both the TGF alpha and c-myc transgenes. This indicates that there is a requirement for the presence of both proteins for transformation of these glands. In summary, TGF alpha and c-Myc synergize in an extremely powerful way to cause breast and salivary gland tumorigenesis in males and virgin females without a requirement for pregnancies. | ||||||||||||
Links |
J:29599 – MGI References 7669729 – National Library of Medicine/PubMed |
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Strain Notes
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| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| STOCK Tg(MtTGFA)100Lmb Tg(MMTV-Myc)141-3Led | Mammary gland adenocarcinoma |
|
Mammary gland |
100 |
|
| STOCK Tg(MtTGFA)100Lmb Tg(MMTV-Myc)141-3Led | Mammary gland adenocarcinoma |
|
Mammary gland |
100 |
|
| STOCK Tg(MMTV-Myc)141-3Led | Mammary gland adenocarcinoma | Mammary gland |
observed - 50 |
||
| STOCK Tg(MtTGFA)100Lmb | Mammary gland cyst | Mammary gland |
observed |
||
| STOCK Tg(MMTV-Myc)141-3Led | Mammary gland cyst | Mammary gland |
observed |
||
| STOCK | Mammary gland cyst | Mammary gland |
observed |
||
| STOCK Tg(MMTV-Myc)141-3Led | Mammary gland hyperplasia - atypical | Mammary gland |
observed |
||
| FVB/N-Tg(MtTGFA)100Lmb | Mammary gland tumor | Mammary gland |
observed |
||
| CD-1;B6-Tg(MMTV-Myc)141-3Led | Mammary gland tumor | Mammary gland |
observed |
||
| STOCK Tg(MtTGFA)100Lmb | Mammary gland tumor | Mammary gland |
0 |
||
| STOCK Tg(MMTV-Myc)141-3Led | Mammary gland tumor | Mammary gland |
0 |
||
| STOCK | Mammary gland tumor | Mammary gland |
0 |
||
| STOCK Tg(MtTGFA)100Lmb Tg(MMTV-Myc)141-3Led | Salivary gland - Parotid adenocarcinoma | Salivary gland - Parotid |
observed |
||
| STOCK Tg(MtTGFA)100Lmb Tg(MMTV-Myc)141-3Led | Salivary gland - Parotid adenoma | Salivary gland - Parotid |
observed |
||
| STOCK Tg(MtTGFA)100Lmb | Salivary gland - Sublingual hyperplasia | Salivary gland - Sublingual |
observed |
||
| STOCK Tg(MMTV-Myc)141-3Led | Salivary gland - Sublingual metaplasia - serous | Salivary gland - Sublingual |
observed |
||
| STOCK Tg(MtTGFA)100Lmb Tg(MMTV-Myc)141-3Led | Salivary gland - Sublingual metaplasia - squamous | Salivary gland - Sublingual |
observed |
||
| STOCK Tg(MtTGFA)100Lmb | Salivary gland - Sublingual metaplasia - squamous | Salivary gland - Sublingual |
observed |
||
| STOCK Tg(MtTGFA)100Lmb | Salivary gland - Submandibular hyperplasia | Salivary gland - Submandibular |
observed |
||
| STOCK Tg(MtTGFA)100Lmb | Salivary gland - Submandibular metaplasia - squamous | Salivary gland - Submandibular |
observed |
||
| STOCK Tg(MtTGFA)100Lmb Tg(MMTV-Myc)141-3Led | Salivary gland hyperplasia | Salivary gland |
100 |
||
| STOCK Tg(MtTGFA)100Lmb | Salivary gland hyperplasia | Salivary gland |
observed |
||
| STOCK Tg(MMTV-Myc)141-3Led | Salivary gland hyperplasia | Salivary gland |
0 |
||
| STOCK | Salivary gland hyperplasia | Salivary gland |
0 |
||
| STOCK | Salivary gland metaplasia | Salivary gland |
0 |
||
| STOCK Tg(MtTGFA)100Lmb | Salivary gland tumor | Salivary gland |
0 |
||
| STOCK Tg(MMTV-Myc)141-3Led | Salivary gland tumor | Salivary gland |
0 |
||
| STOCK | Salivary gland tumor | Salivary gland |
0 |