Progression of Pregnancy-Dependent Mouse Mammary Tumors after Long Dormancy Periods. Involvement of Wnt Pathway Activation

Autor: Lucio H. Castilla, Carolina Schere-Levy, Albana Gattelli, María Julieta Binaghi, Roberto Meiss, Ana Quaglino, María Cecilia Cirio, Edith C. Kordon, Natalia J. Martinez
Rok vydání: 2004
Předmět:
Cancer Research
medicine.medical_specialty
Neoplasms
Hormone-Dependent
Time Factors
medicine.drug_class
Fibroblast Growth Factor 3
Molecular Sequence Data
Mammary gland
Population
Apoptosis
Biology
Wnt2 Protein
Mice
Pregnancy
Proto-Oncogene Proteins
Internal medicine
medicine
Animals
education
Receptor
Mice
Inbred BALB C
education.field_of_study
Base Sequence
Mouse mammary tumor virus
Wnt signaling pathway
Mammary Neoplasms
Experimental
Cell Differentiation
Epithelial Cells
biology.organism_classification
Fibroblast Growth Factors
medicine.anatomical_structure
Endocrinology
Mammary Tumor Virus
Mouse
Receptors
Estrogen
Oncology
Estrogen
Genetically Engineered Mouse
Mutation
Disease Progression
Cancer research
Female
Signal transduction
Receptors
Progesterone
Pregnancy Complications
Neoplastic
Cell Division
Neoplasm Transplantation
Signal Transduction
Zdroj: Cancer Research. 64:5193-5199
ISSN: 1538-7445
0008-5472
Popis: Mouse mammary tumor virus (LA) induces pregnancy-dependent mammary tumors that progress toward autonomy. Here we show that in virgin females, pregnancy-dependent tumor transplants are able to remain dormant for up to 300 days. During that period, these tumors synthesize DNA, express high levels of estrogen and progesterone receptors (ER+PR+) and are able to resume growth after hormone stimulation. Surprisingly, in a subsequent transplant generation, all these tumors are fully able to grow in virgin females, they express low levels of ER and PR (ER−PR−) and have a monoclonal origin; i.e., show all of the features we have described previously in pregnancy-independent tumors. Histologically, mouse mammary tumor virus (LA)-induced tumors are morphologically similar to genetically engineered mouse (GEM) mammary tumors that overexpress genes belonging to the Wnt pathway. Interestingly, in the virus-induced neoplasias, pregnancy-independent passages arising after a dormant phase usually display a lower level of glandular differentiation together with epithelial cell trans-differentiation, a specific feature associated to Wnt pathway activation. In addition, dormancy can lead to the specific selection of Int2/Fgf3 mutated and overexpressing cells. Therefore, our results indicate that during hormone-dependent tumor dormancy, relevant changes in cell population occur, allowing rapid progression after changes in the animal internal milieu.
Databáze: OpenAIRE
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