Suppression of parathyroid hormone-related protein messenger RNA expression by medroxyprogesterone acetate in breast cancer tissues

The level of parathyroid hormone-related protein (PTHrP) expressed in breas t cancer tissue is closely related to the incidence of bone metastasis. We examined the PTHrP mRNA expression in breast cancer tissues by coamplificat ion polymerase chain reaction (PCR) in mole ratio to internal standard beta -actin mRNA. The PTHrP expression was higher in premenopausal patients than in postmenopausal patients (P < 0.05). More pronounced difference by menop ause found in estrogen receptor (ER) positive groups (P < 0.001) indicated that the PTHrP expression in breast cancer tissue is hormonally regulated a nd might be altered by endocrine agents. To clarify the changes of PTHrP ex pression by endocrine therapy of breast cancer, we measured PTHrP expressio n in the breast cancer tissue incubated for 24 h with 1 x 10(-8) M of estra diol (E2), 1 x 10(-6) M of tamoxifen (TAM) and 1 x 10(-5) M of medroxyproge sterone acetate (MPA). The PTHrP expression was decreased significantly by MPA (P < 0.005), while E2 and TAM did not change the PTHrP expression. Prog esterone receptor (PgR) mRNA expression was also examined to confirm that t he breast cancer tissue responds to E2 and TAM. The results were well compa tible with the better therapeutic effect of MPA reported for the treatment of breast cancer with bone metastases. As a potential candidate for the rec eptor that mediates the suppressive effect of MPA, androgen receptor (AR) i s suggested most probable. Present results also demonstrated that the clini cal response of individual tumors is closely associated with the early in v itro changes of gene expression detected in the cancer specimen.