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 breast cancer tissue is closely related to the incidence of bone metastasis. We examined the PTHrP mRNA expression in breast cancer tissues by coamplification 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 menopause found in estrogen receptor (ER) positive groups (P < 0.001) indicated that the PTHrP expression in breast cancer tissue is hormonally regulated and might be altered by endocrine agents. To clarify the changes of PTHrP expression by endocrine therapy of breast cancer, we measured PTHrP expression in the breast cancer tissue incubated for 24 h with 1 x 10(-8) M of estradiol (E2), 1 x 10(-6) M of tamoxifen (TAM) and 1 x 10(-5) M of medroxyprogesterone acetate (MPA). The PTHrP expression was decreased significantly by MPA (P < 0.005), while E2 and TAM did not change the PTHrP expression. Progesterone receptor (PgR) mRNA expression was also examined to confirm that the breast cancer tissue responds to E2 and TAM. The results were well compatible with the better therapeutic effect of MPA reported for the treatment of breast cancer with bone metastases. As a potential candidate for the receptor that mediates the suppressive effect of MPA, androgen receptor (AR) is suggested most probable. Present results also demonstrated that the clinical response of individual tumors is closely associated with the early in vitro changes of gene expression detected in the cancer specimen.
Sugimoto
T
T
Department of Surgical Oncology, Osaka University Medical School, Suita, Japan.
Shiba
E
E
Watanabe
T
T
Takai
S
S
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004958:Estradiol; D017258:Medroxyprogesterone Acetate