Table 1.

Representative genetically-engineered mouse models of prostate cancer

Mouse Model	Strengths	Limitations	References
Group 1: SV40 transgenic models
TRAMP model Minimal probasin promoter driving SV40 large and small T antigens	One of the first prostate cancer models developed Prostate specific phenotype Progression from PIN to cancer and metastases Displays castration- resistant disease High penetrance and predictable tumor growth Crosses with many other models has informed on disease mechanisms	Tumors primarily neuroendocrine in origin Promoter dependent on androgens Rarely metastasizes to bone Relatively short kinetics differ from the characteristically slow development in humans	[10–12, 121]
LADY model Large probasin promoter driving SV40 large T antigen	Promoter has higher expression levels Progression from PIN to carcinoma Progression slower than TRAMP mice	Distant metastases are rare Primarily PIN, although 12T-10 line develops neuroendocrine phenotype	[31, 122]
T121 Model: Minimal probasin promoter driving SV40 small T antigen	Provides insight on pRB function Phenotype accelerated when combined with Pten	Does not model metastases	[35]
Group 2: Oncogene transgenic models
c-Myc models Probasin promoter driving c-Myc Lo-Myc Hi-Myc	Adenocarcinoma rather than neuroendocrine tumors Progression from PIN to invasive adenoarcinoma	Promoter dependent on androgens Does not metastasize	[43]
TMPRSS-ERG models: Probasin promoter driving expression of ERG or ETV1	Functional analyses of a key translocation event Cooperates with Pten loss of functions	Different phenotypes observed merits further clarification	[48–52]
Akt model Probasin promoter driving activated form of Akt	Models Akt activation	Relatively weak phenotype compared with other models of this pathway	[53]
Group 3: Developmental pathways and androgen receptor signaling
Nkx3.1 Germline loss of function; conditional loss of function	Models prostate cancer initiation Cooperates with Pten loss	Does not progress to cancer	[59, 61, 123]
Wnt/β-Catenin Probasin Cre to drive conditional inactivation of APC or β-Catenin	Modeling Wnt signaling in mice	No distant metastases	[75, 76]
FGFR1 Chimeric protein having dimerization motif attached to FGFR1	Models cancer progression Allows for inducible and reversible expression	May be limited to receptor activation	[71]
TGFβ Stromal-Cre to conditionally inactivate TGFβ	Model of stromal interactions in prostate cancer	Stromal promoters not specific for prostate	[78]
Androgen receptor Probasin promoter to express wild-type or mutated androgen receptor	Model to study androgen receptor function in prostate epithelium	Conflicting reports need further clarification Need to distinguish from stromal from epithelial role of androgen receptor	[81, 83]
Group 4: Pten tumor suppressor models
Pten germline	Principal driving event in prostate cancer in mice Displays cancer progression Cooperates with various other factors in cancer progression	Other cancer phenotypes confound analyses of prostate phenotype	[88, 89]
Pten germline combined with: Nkx3.1 p27 Myc	Cooperative phenotypes in cancer progression Molecular insights into pathways of progression Rare metastases in aged mice	Other cancer phenotypes confound analyses of prostate phenotype	[102–104, 107]
Pten conditional Probasin Cre to conditionally inactivate Pten in prostate	Principal driving event in prostate cancer in mice PIN to microinvasive phenotypes Has been crossed with many other alleles to investigate their contribution to disease progression	Develop senescence that limits cancer progression Do not develop metastases	[92, 95]
Pten inducible Nkx3.1CreERT2 or PSA CreERT2 to inducibly inactivate Pten in prostate	Regulated expression in adult prostate PIN to microinvasive phenotypes Castration alleviates senescence phenotype	Do not develop metastases Tamoxifen induction may affect prostate phenotype	[97, 98]
Pten; p53 conditional Probasin Cre to conditionally inactivate Pten and p53 in prostate	Lethal prostate tumors p53 loss overrides senescence phenotype	Do not develop metastases	[96]
Pten; Smad4 Probasin Cre to conditionally inactivate Pten and SMAD4 in prostate	Lethal prostate tumors with metastases Signature of prognostic value	Low penetrance of metastases	[111]
Pten; Braf Nkx3.1CreERT2 to inducibly inactivate Pten and activate Braf in prostate	Lethal prostate tumors with metastases Myc pathway activation	Does not develop metastases to bone	[115]
Pten; Kras Nkx3.1CreERT2 to inducibly inactivate Pten and activate Kras in prostate	Lethal prostate tumors Fully penetrant metastatic phenotype	Does not develop metastases to bone	[117]