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Animal models relevant to human prostate carcinogenesis underlining the critical implication of prostatic stem/progenitor cells

Authors :
Murielle Mimeault
Surinder K. Batra
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.

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