Preclinical Remodeling of Human Prostate Cancer through the PTEN/AKT Pathway

Table 1

Traditional Pten knockout mouse models of prostate cancer.

Description	Gene knockout level	Pten mutation locus	Mouse strain	Phenotype	Castration resistance	Comments	Year	Ref.
Pten^+/−	Single	Exons 4 and 5	129SvJy/C57BL/6	PIN	Not reported	Pten^−/− progeny were nonviable; multiple organ neoplasia in Pten^+/− mutants	1998	[46]
Pten^+/−	Single	Exon 5	129SvJy/C57BL/6	PIN	Not reported	Pten^−/− progeny were nonviable; multiple organ neoplasia in Pten^+/− mutants	1999	[47]
Pten^+/−/Cdkn1b^−/−	Compound	Exon 5	C57BL/6	Invasive adenocarcinoma	Not reported	Rapid progression of invasive carcinoma and decreased survival	2001	[48]
PTEN^+/−/TRAMP	Compound	Exon 5	129SvJy/C57BL/6	Metastatic neuroendocrine carcinoma	Not reported	Increased rate of tumor development and metastases	2001	[49]
Ink4a/Arf^−/−/Pten^+/-	Compound	Exon 5	FVB/n/C57BL/6	PIN	Not reported	Early onset of PIN lesionsMultiple organ neoplasia and reduced tumor-free survival	2002	[50]
Pten^+/-/Nkx3.1^+/-	Compound	Exon 5	129SvJy/C57BL/6	Metastatic adenocarcinoma to lymph nodes	Yes	Mice developed adenocarcinomas in the dorsolateral prostate at 12 months and androgen independent phenotypes following castration	2003	[51–53]
Pten^+/−/Akt1^−/−	Compound	Exons 4 and 5	129SvJy/C57B6	PIN	Not reported	Akt deficiency attenuated PIN development	2006	[54]
Pten^+/− PB-ERG	Compound	Exons 4 and 5	129SvJy/C57BL/6	Invasive adenocarcinoma	Not reported	Overexpression of ERG cooperates and Pten haploinsufficiency leads to invasive adenocarcinoma and reduced cancer latency	2009	[55]
ARR2Pb.Stat3C/ PTEN^+/−	Compound	Exon 5	FVB/n/C57BL/6	Invasive adenocarcinoma	Not reported	Increased incidence of AdCa in the ventral lobe	2011	[56]