Alternative mammary oncogenic pathways are induced by D-type cyclins; MMTV-cyclin D3 transgenic mice develop squamous cell carcinoma
| Autor: | Paul Waring, Joy Hendley, Anne Thompson, Doris Germain, Kerry Warren, Renee Dow, Andreja Pirkmaier, Soula Ganiatsas |
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| Rok vydání: | 2003 |
| Předmět: |
Cancer Research
medicine.medical_specialty Squamous Differentiation Cyclin D Muscle Proteins Mice Transgenic Biology Mice Cyclin D1 Mammary tumor virus Internal medicine Cyclins Genetics medicine Animals Cyclin D3 Molecular Biology Cyclin-Dependent Kinase Inhibitor p16 Cyclin Microfilament Proteins Mammary Neoplasms Experimental medicine.disease Squamous metaplasia Endocrinology Mammary Tumor Virus Mouse Cancer research biology.protein Carcinoma Squamous Cell Female Cyclin A2 |
| Zdroj: | Oncogene. 22(28) |
| ISSN: | 0950-9232 |
| Popis: | The three human D-type cyclins, cyclin D1, D2 and D3 share the ability to bind to and activate cdk4 and 6. MMTV-cyclin D1 transgenic mice develop mainly adenocarcinoma, while MMTV-cyclin D2 mice show a lack of alveologenesis during pregnancy and only develop carcinoma at low frequency. The effect of cyclin D3 overexpression in mammary glands remains hitherto unknown. We generated MMTV-cyclin D3 transgenic mice and report here that they develop exclusively squamous cell carcinoma. We show that although cyclin D3 transgene expression was detected early in puberty, postnatal development and mammary gland proliferation were normal in virgin animals. In contrast, multiparous mice develop multiple foci of abnormal growth that correspond to various stages of squamous metaplasia. Therefore, our results support a role for cyclin D3 in squamous differentiation. In addition, we found that p16 expression during involution is abolished, while p27 expression increased in MMTV-cyclin D3 mice, two modifications that have been reported in the other MMTV-D-type cyclin transgenic models. Our observations indicate that despite biochemical redundancy in vitro and in vivo, D-type cyclins promote distinct oncogenic pathways. |
| Databáze: | OpenAIRE |
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