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

Table 2

Conditional Pten knockout mouse models of prostate cancer.

Description	PTEN genetic manipulation	Gene knockout level	Pten mutation locus	Mouse strain	Phenotype	Castration resistance	Comments	Year	Ref.
PB^Cre4/Pten^loxp/loxp	Conditional	Single	Exons 4 and 5	129SvJy/C57BL/6	Homozygous deletion results in invasive adenocarcinoma and metastatic spread to lymph nodes	Not reported	ARR2PB-Cre promoter-driven; 100% of mice developed invasive carcinoma at 6 months	2003	[84]
PB^Cre4/Pten^loxp/loxp	Conditional	Single	Exon 5	C57BL/6/DBA2; /129/BALB/c	Homozygous deletion results in invasive adenocarcinoma and metastatic spread to lymph nodes	Yes	ARR2PB-Cre promoter-driven; Pin lesions develop at 6 weeks and invasive adenocarcimoa by 9 weeks	2003	[85]
MMTVCre/PTEN^loxp/loxp	Conditional	Single	Exons 4 and 5	C57BL/6	Homozygous deletion results in invasive adenocarcinoma	Not reported	MMTV-Cre promoter-driven; focally invasive carcinoma at 10 weeks Mice die from lymphomas at 14 wks	2004	[89]
PSA^Cre/Pten^loxp/loxp	Conditional	Single	Exon 5	FVB/n/129Ola	Invasive adenocarcinoma	Not reported	PSA-Cre promoter-driven; all mice develop adenocarcinoma at 10–14 months with rare metastases	2005	[86]
PSA^Cre/Pten^loxp/loxp	Conditional	Single	Exons 4 and 5	C57BL/6	Homozygous deletion results in invasive adenocarcinoma and metastatic spread to lymph nodes	Yes	PSA-Cre promoter-driven; 50% incicence of adenocarcinoma at 10 weeks, lymph node metastasis >12 months	2012	[a]
Pb-Cre4/Pten^loxP/loxP/; Trp53^loxP/loxP	Conditional	Compound	Exons 4 and 5	129SvJy/C57BL/6	Homozygous deletion results in invasive adenocarcinoma	Not reported	ARR2PB-Cre promoter-driven; invasive adenocarcinoma at 4–6 months with mean survival of 5 months	2005	[88]
PB^Cre4/Pten^+/loxP/ FGF8b	Conditional	Compound	Exon 5	C57BL/6/DBA2x; 129/BALB/c	Homozygous deletion results in invasive adenocarcinoma and metastatic spread to lymph nodes	Not reported	ARR2PB-Cre promoter-driven; activation of FGF8b and heterozygous loss of Pten cooperate in the late-onset induction of metastatic prostate cancer with high incidence	2006	[87]
PSA^CreERT2/Pten^loxp/loxp	Inducible conditional	Single	Exons 4 and 5	129SvJy/C57BL/6/ FVB/n	Homozygous deletion results in invasive adenocarcinoma after tamoxifen treatment	Not reported	Tam-inducible Cre-ERT2 recombinase under the control of the human PSA proximal promoter	2008	[90]
Nkx3.1^CreERT2/ Pten^loxp/loxp	Inducible conditional	Single	Exon 5	C57BL/6/129/Sv	Homozygous deletion results in invasive adenocarcinoma after tamoxifen treatment	Yes	Tam-inducible Cre-ERT2 recombinase under the control of the Nkx3.1 promoter	2009	[91]

^aDe Velasco et al. [95].