The relationship of BRMS1 and RhoGDI2 gene expression to metastatic potential in lineage related human bladder cancer cell lines

We have recently characterized a human bladder cancer cell line T24 and a m ore aggressive lineage related variant of it, T24T. To gain further insight s, we have studied their metastatic ability in an in vivo model system. Res ults show that T24 forms significantly fewer [4/12 (1/11) mice had metastas es with 1-2 lesions/mouse] metastasis in SCID/bg mice than T24T [14/14 (6/6 ) mice had metastases with a mean of 24-28 lesions/mouse]. To begin explori ng the mechanisms underlying this difference, we evaluated the mRNA and pro tein expression levels of metastasis-suppressor genes, known to be importan t in the progression of other cancers, in our model of bladder cancer progr ession. A higher mRNA expression of BRMS1, a metastasis suppressor in breas t cancer, was observed in T24 cells. In addition, RhoGDI2 mRNA expression w as only observed in T24 when compared to T24T, suggesting that Rho activati on might play a significant role in the metastatic cascade. However, a basa l level mRNA expression of KISS1, described as metastasis suppressor in mel anoma and breast, was observed in both the lines and had slightly higher ex pression in T24T. No difference of Nm23-H1, KAI1, MKK4/SEK1 and E-Cadherin protein levels were noted between these two lines. In summary, it appears t hat the T24/T24T paired cell lines constitute a useful model for the study of human bladder cancer metastasis that will allow both the discovery and m echanistic evaluation of genes potentially involved in this process.