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Abstract It is the most common cause of cancer among females in both developed and developing countries, and is responsible for over 1 million of the estimated 10 million neoplasms diagnosed worldwide each year in both. Nearly a third of all new cancers in females are breast cancers. The incidence rates generally increase with age, with the greatest rate of increase prior to the menopause, supporting a link with hormonal status. The major skeletal complications of breast cancer are hypercalcemia and bone metastasis. It is unique among malignancies due to the high rate of developing osteolytic bone metastases (in about 70% of patients). Bone as a target for metastasis presents a particularly harsh environment for the establishment and proliferation of cancer cells. In addition to their general invasive properties, malignant cells can adhere to the bone surface and promote the formation of active osteoclasts from precursors in the host bone marrow, thereby initiating resorption and allowing the tumor to establish and expand. PTH-rP was discovered in 1982 by Broadus et al. during the search for the circulating factors secreted by tumors which causes the common paraneoplastic syndrome (humoral hypercalcemia of malignancy). The cloning of the DNA was in 1987. Many studies demonstrated the expression of PTH-rP in several tissues. It was found to be present at the morula stage of the embryos. It has profound effects on a large number of physiologic processes and deletion of its gene has lethal consequences. Most breast cancer cells secrete higher levels of PTH-rP than do normal breast cells. In fact, it has been proposed that PTH-rP production may be one of the key elements in supporting carcinogenesis. . Positive PTH-rP status in the primary breast cancers is independently associated with improved survival with reduced metastases to all tissues including bone. The 5-year survival rate were 87% for patients with PTHrP-positive tumors and 73% for PTHrP-negative tumors. PTH-rP might indeed confer on cancer cells a less invasive phenotype. Strategies aimed at blocking PTHRP-R activation may therefore slow the progression of breast cancer cells in bone metastasis. Treatment with bisphosphonates will prevent bone resorption and reduce the release of bone growth factors. Ongoing research will reveal much more additional effects about that highly important protein. |