Complete LKB1 loss results in lethal metastatic prostate cancer

In order to identify the contribution of Lkb1 loss to Pten driven prostate cancer progression, we engineered a prostate conditional mutant mice in which was induced the loss of Lkb1 in combination with heterozygous loss of the prostate tumor suppressor Pten (Ptenpc+/- Lkb1pc-/-). This mouse model developed metastatic prostate squamous cell carcinoma. We compared this tumor type with the adenocarcinomas developed in Ptenpc-/- Lkb1pc+/+ mice. We carried out microdissection and RNA extraction of tumor tissues embedded in paraffin of Ptenpc+/- Lkb1pc-/- and Ptenpc-/- Lkb1pc+/+. To distinguish between early and late phenotype of prostate squamous cell carcinoma, we compared Ptenpc+/- Lkb1pc-/- tumor tissues collected at the age of six and ten months of age among them and with Ptenpc-/- Lkb1pc+/+ mouse prostate tissue. Gene expression was compared among prostate tumors generated in Ptenpc+/- Lkb1pc-/- and Ptenpc-/- Lkb1pc+/+ mouse models. Specifically, early (six months) and late (ten months) stages of carcinomas developed in Ptenpc+/- Lkb1pc-/- mice were compared with prostate adenocarcinoma originated in Ptenpc-/- Lkb1pc+/+ mice. In this transcriptomic study, we included 4 samples of early stage prostate carcinomas (Ptenpc+/- Lkb1pc-/-), 4 samples of late stage prostate carcinomas (Ptenpc+/- Lkb1pc-/-) and 5 samples of prostate adenocarcinomas (Ptenpc-/- Lkb1pc+/+).