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Animal models relevant to human prostate carcinogenesis underlining the critical implication of prostatic stem/progenitor cells
- Source :
- Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1816:25-37
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Recent development of animal models relevant to human prostate cancer (PC) etiopathogenesis has provided important information on the specific functions provided by key gene products altered during disease initiation and progression to locally invasive, metastatic and hormone-refractory stages. Especially, the characterization of transgenic mouse models has indicated that the inactivation of distinct tumor suppressor proteins such as phosphatase tensin homolog deleted on chromosome 10 (PTEN), Nkx3.1, p27 KIP1 , p53 and retinoblastoma (pRb) may cooperate for the malignant transformation of prostatic stem/progenitor cells into PC stem/progenitor cells and tumor development and metastases. Moreover, the sustained activation of diverse oncogenic signaling elements, including epidermal growth factor receptor (EGFR), sonic hedgehog, Wnt/β-catenin, c-Myc, Akt and nuclear factor-kappaB (NF-κB) also may contribute to the acquisition of more aggressive and hormone-refractory phenotypes by PC stem/progenitor cells and their progenies during disease progression. Importantly, it has also been shown that an enrichment of PC stem/progenitor cells expressing stem cell-like markers may occur after androgen deprivation therapy and docetaxel treatment in the transgenic mouse models of PC suggesting the critical implication of these immature PC cells in treatment resistance, tumor re-growth and disease recurrence. Of clinical interest, the molecular targeting of distinct gene products altered in PC cells by using different dietary compounds has also been shown to counteract PC initiation and progression in animal models supporting their potential use as chemopreventive or chemotherapeutic agents for eradicating the total tumor cell mass, improving current anti-hormonal and chemotherapies and preventing disease relapse.
- Subjects :
- Male
Cancer Research
Antigens, Polyomavirus Transforming
Mice, Transgenic
medicine.disease_cause
CXCR4
Article
Mice
Prostate cancer
Cancer stem cell
Genetics
medicine
Animals
Humans
Regeneration
PTEN
Progenitor cell
PI3K/AKT/mTOR pathway
biology
PTEN Phosphohydrolase
Wnt signaling pathway
Prostatic Neoplasms
Oncogenes
medicine.disease
Disease Models, Animal
Oncology
Immunology
Neoplastic Stem Cells
biology.protein
Cancer research
Carcinogenesis
Subjects
Details
- ISSN :
- 0304419X
- Volume :
- 1816
- Database :
- OpenAIRE
- Journal :
- Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
- Accession number :
- edsair.doi.dedup.....8a1a203e86ed64e3e72b2a1ea54e55a4
- Full Text :
- https://doi.org/10.1016/j.bbcan.2011.03.001