Our study aimed at understanding the regulation of parathyroid hormone related peptide (PTHRP) by androgens in prostate cancer. Although PTHRP has been identified as a factor responsible for malignancy-associated hypercalcemia, it is known to be widely expressed in normal tissues where it regulates cellular growth and differentiation. PTHRP binds with equal affinity and activates the membrane-embedded G protein-coupled PTH/PTHRP receptor present on the surface of target cells such as bone and kidney. Upon receptor binding several signaling pathways are activated including the adenylyl cyclase and the phospholipase C pathways. / A number of growth factors and steroid hormones have previously been shown to regulate PTHRP production. To study the regulation of PTHRP by androgens, we used a late stage human prostate cancer cell line that is androgen non-responsive, PC-3 cells. In addition, we used an androgen responsive cell line, transfected with a functional androgen receptor, PC-3T cells. Results obtained by Northern blots and immunoradiometric assays demonstrated that androgens inhibit PTHRP expression in this human prostate cancer system. Male Balb/c nu/nu mice, injected subcutaneously with PC-3 cells, developed larger tumors than experimental animals inoculated with PC-3T cells. Moreover, castration of the host animals resulted in the substantial increased in PC-3T tumor volumes. Immunohistochemical studies indicated that PTHRP expression was inhibited in experimental PC-3T tumors and that castration of animals increased PTHRP production. In conclusion, our study demonstrated that androgens down regulate PTHRP production in prostate cancer cells in vitro and that prostate tumor cells producing less PTHRP exhibited a reduction in tumor volume in vivo.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33824 |
| Date | January 2001 |
| Creators | Pizzi, Helena. |
| Contributors | Goltzman, David (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001862490, proquestno: MQ78941, Theses scanned by UMI/ProQuest. |
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