Phenotypes Associated with This Genotype

Genotype
MGI:5543907

• Allelic Composition: Braf^tm1Mmcm/Braf^tm1Mmcm; Nkx3-1^{tm4(cre/ERT2)Mms}/Nkx3-1⁺; Pten^tm1Hwu/Pten⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

neoplasm

increased prostate gland tumor incidence ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

♂ • tumors are large and highly proliferative and are primarily composed of luminal epithelial cells

♂ • tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration

♂ • tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative

♂ • treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation

increased prostate gland adenocarcinoma incidence ( J:191327 )

♂ • tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction

increased prostate intraepithelial neoplasia incidence ( J:191327 )

♂ • tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

increased metastatic potential ( J:191327 )

♂ • metastases to lungs and lymph nodes are seen in tamoxifen treated mutants and disseminated tumor cells are seen in the bone marrow

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

♂ • tumors are large and highly proliferative and are primarily composed of luminal epithelial cells

♂ • tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration

♂ • tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative

♂ • treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation

increased prostate gland adenocarcinoma incidence ( J:191327 )

♂ • tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction

increased prostate intraepithelial neoplasia incidence ( J:191327 )

♂ • tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

reproductive system

increased prostate gland tumor incidence ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

♂ • tumors are large and highly proliferative and are primarily composed of luminal epithelial cells

♂ • tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration

♂ • tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative

♂ • treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation

increased prostate gland adenocarcinoma incidence ( J:191327 )

♂ • tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction

increased prostate intraepithelial neoplasia incidence ( J:191327 )

♂ • tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:191327