FOLATE RECEPTORS AS POTENTIAL THERAPEUTIC TARGETS IN CHOROID-PLEXUS TUMORS OF SV40 TRANSGENIC MICE

A high affinity folate receptor is expressed in some human cancers, in cluding choroid plexus tumors and ependymomas, and has been suggested as a target for therapeutics. In this report, the expression of folate receptors in an SV40 large T antigen transgenic mouse (SV11) was inve stigated. SV11 mice develop choroid plexus tumors, a property that may be related to the observation that SV40 has been isolated from human choroid plexus tumors and ependymomas. We report that SV11 choroid ple xus tumors contain a high affinity folate receptor (K-D of 1 nM), dete ctable by I-125-folate autoradiography and immunohistochemistry. Weste rn blot analysis indicated an apparent molecular weight of 38 kDa. RT- PCR revealed the presence of transcripts for both alpha and beta isofo rms of the folate receptor. Brain parenchyma has undetectable folate r eceptor, but normal choroid plexus has substantial levels (as does hum an choroid plexus). The folate receptors of the tumor are accessible f rom the bloodstream whereas those of the normal choroid plexus are not . Thus SV11 transgenic mice should be useful for evaluating therapeuti c targeting of high affinity folate receptors, both for efficacy of sp ecific agents and possible side effects.