Expression of the calcium-binding protein S100A4 (p9Ka) in MMTV-neu transgenic mice induces metastasis of mammary tumours.

Increased levels of S100A4 (p9Ka) confer metastatic ability on a normally non-metastatic epithelial cell line. To find out whether S100A4 can induce metastasis in vivo, transgenic mice expressing high levels of S100A4, but which show no phenotypic effect, have been mated with MMTV-neu transgenic mice which succumb to stochastic mammary neoplasia related to expression of the MMTV-neu transgene. Resultant bitransgenic, multiparous, female progeny expressing both S100A4 and Neu have a slightly earlier incidence of palpable mammary tumours than the MMTV-neu offspring and specifically exhibit macroscopic metastatic lesions in the lungs. The S100A4 transgene is expressed in primary and secondary lesions of bitransgenic offspring and its expression is particularly associated with regions of invasion of primary lesions and metastases.