Differential gene expression in human prostate cancer cells adapted to growth in bone in Beige mice

A metastasis model was used to identify genes potentially related to the growth of human prostate cancer in the bone. Injection of the human prostate cancer line PC3 into the femurs of Beige mice induced tumors that ruptured the femurs in 4 to 6 weeks.

The subline PC3a was cultured in vitro from one of these PC3 bone tumors. PC3a cells were reinjected into femurs, and the subline PC3b was then cultured from a resulting PC3a tumor. Likewise, PC3c was derived from a PC3b bone tumor. The PC3 tumors were osteolytic, invasive and metastatic.

Analysis of gene expression in these PC3 sublines by differential-display RT-PCR identified two groups of transcripts whose steady state levels differed substantially from the original PC3 line. One group of transcripts increased with progressive adaptation to tumor formation in bone. The second group showed the reverse pattern. They progressively diminished in subsequent sublines, and were virtually absent in PC3b and PC3c. Two in this group were fibroblast growth factor receptor-2 and caveolin-1. They were strongly expressed in non-malignant prostate tissue.

These two downregulated genes, which have been reported to play a role in the development of androgen independence and malignant progression, may reflect molecular changes in growth regulation of PC3 cells during readaptation to an intra-osseal environment.