Table 3.

GEMM based on human genomic alteration using different promoters.

Mouse Model	Features	Ref.
Pten-derived mouse model with multiple genetic mutations	Loss of function
Pten+/−	Develop dysplastic intestinal polyps, PIN, and neoplasia in multiple tissues. Most die within 8 months due to massive lymph-splenomegaly. The survivor PTEN+/− mice display PIN lesions by 10 months. No invasive and metastatic adenocarcinoma.	[89][88]
Ptenflox/flox(exon 4,5)/PBCre4	Develop HGPIN in 9 weeks, followed by carcinoma in 17-26 weeks. No metastasis up to 130 weeks.	[90]
Ptenflox/flox(exon 5)/PBCre4	Develop prostatic epithelial hyperplasia by 4 weeks, PIN in 6 weeks, and adenocarcinoma by 9-29 weeks. Metastasize to lung and lymph nodes by 12 weeks.	[95]
Pten+/−;p27−/−	Develop PCa at complete penetrance within 12 weeks from birth. No metastasis	[167]
Pten+/−; Nkx3.1−/−	Develop HGPIN by 6 months of age and ultimately progress to adenocarcinoma.	[117]
Pten+/−; Nkx3.1+/−p27+/− or Pten+/−; Nkx3.1+/−p27−/−	PCa progression is enhanced by the loss of one wildtype p27kip1 allele but inhibited by the loss of both alleles.	[97]
NPKEYFP mice (Nkx3.1CreERT2/+; Ptenflox/flox; KrasLSL-G12D/+; R26R-CAG LSL-EYFP/+	Tumor formation at 2- 3 months of age by tamoxifen administration and micro-metastasis at 5-8 months.	[102]
Pten−/+; Trp53−/− (RapidCap- model)	Metastasis to distant sites at greater than 50% penetrance by four months.	[105]
NPp53 mice (Ptenflox/flox; Trp53flox/flox; Nkx3.1CreERT2)	Under castrate, develops CRPC characteristics and, after treatment with abiraterone, displays NEPC features.	[109]
Ptenflox/flox: Rbflox/flox/ PBCre4 (DKO model)	Develops PIN and early invasive carcinoma within 12 weeks. Neuroendocrine features (synaptophysin-positive cells) appear by 20-25 weeks. ADT sensitive because castration extended the median survival of these mice from 38 to 48 weeks, but all mice eventually died from prostate cancer by 67 weeks. Median survival 38 weeks. Develops metastasis in the lymph nodes, liver, and lung.	[122]
Ptenflox/flox;Rbflox/flox;Trpflox/flox/ PBCre4 (TKO model)	Develops castration-resistant tumors, survival rate 16 weeks. ADT-resistance because castration of these mice at 10 weeks did not extend survival. These TKO tumors have reduced dependence on both AKT and AR signaling.	[122]
Hi-Myc-derived mouse model with multiple genetic alterations	Conditional Gain of function
Hi-Myc/ARR2PB; Hepsin	Invasive adenocarcinoma at 4.5 months. This model develops a higher-grade adenocarcinoma in 12- to 17-month-old mice. Tumors showed higher hepsin expression. The proposed mechanism is basement membrane degradation. No metastasis.	[168]
Hi-Myc/ARR2PB; IκBa+/−	Develops adenocarcinoma at 26 weeks. PCa progression to CRPC. The proposed mechanism is the activation of NF-κB signaling by regulating AR action.	[169]
Z-Myc-derived mouse model with multiple genetic alterations	Conditional loss of function
Z-Myc/PBcre4; PtenFl/Fl	HGPIN/cancer lesions and promote faster prostate tumorigenesis. The proposed mechanism is a bypass from senescence to apoptosis by repressing the p53 target gene p21Cip1.	[170]
Z-Myc/CMV-β-actin; Nkx3.1	HGPIN with microinvasion. MYC knockdown dysregulates shared NKX3.1/MYC target gene expression. The enhanced MYC transcriptional activity.	[171]
Z-Myc/PBcre4; Pten+/−;TrP53−/−	PIN and adenocarcinoma (10-24 weeks) with marked heterogeneity within the same prostate glands. It accelerates tumor formation and leads to lymph node metastases.	[172]
BMPC model (Hoxb13-Myc;Hoxb13-Cre PtenFl/Fl)	Develops lethal adenocarcinoma with distant metastases. BMPC cancers are deficient in neuroendocrine/ or sarcomatoid differentiation. Induce genomic instability and aggressive prostate cancer similar to human disease at the histologic and genomic levels.	[98]
Other models	Conditional modulation of gene expression
Trp53−/−; Rb−/−	PIN lesions at 8 weeks. Poorly differentiated neuroendocrine features by ~32 week Tumors are ADT-resistant de novo because castration does not extend survival.	[73]
Trp53R270H/+ Nkx3.1Cre	PIN as early as 5 weeks, well-developed neoplastic foci as early as 4 months. Displays invasive adenocarcinoma with epithelial-mesenchymal transition (EMT) phenotype.	[108]
Tmprss2-Erg fusion/Pten−/+	Acceleration of HGPIN and progression to prostatic adenocarcinoma at 6 months. The proposed mechanism is by modulating AR signaling and checkpoint genes.	[135]
Spop/Pten−/+	Develops early neoplastic lesions (HGPIN) with striking nuclear atypia and invasive poorly differentiated carcinoma. Activates both PI3K/mTOR and AR signaling.	[138]
PBCre4/Foxa1loxp/loxp	Develops hyperplasia with an extensive cribriform pattern but does not expand toward more advanced phenotypes. Alterations in localization of p63 positive basal cells. Following castration, the conditional knockout Foxa1 retained its androgen sensitivity, and Foxa1-positive cells appeared to be more castration sensitive.	[173]