title: Craniopharyngioma cell growth is promoted by growth hormone (GH) and is inhibited by tamoxifen: involvement of growth hormone receptor (GHR) and IGF-1 receptor (IGF-1R).
abstract: Hormone receptors are related to the biological behavior and recurrence of craniopharyngioma (CP). The effect of therapeutic growth hormone (GH) replacement on CP growth remains largely unclear. We intended to study expression patterns of GH-related receptors in CP, and to study the effect of GH and its mediator, insulin-like growth factor-1 (IGF-1), as well as tamoxifen, on primary CP cell cultures. Primary cell cultures were established from fresh tumor specimens. The expression of GH receptor (GHR) and IGF-1 receptor (IGF-1R) in tumor specimens was studied using immunohistochemistry. Cell cultures were treated with various concentrations of recombinant GH, IGF-1 and tamoxifen. Cell growth promotion or inhibition was assayed using the Trypan blue dye exclusion test of cell viability. Expression of GHR, IGF-1R, phosphorylated-Akt and Akt after treatment was studied using Western blot assay. Twenty-nine primary cultures from 36 patients were established. GHR and IGF-1R were expressed in tumor tissue. The promotion of cell growth by GH compared to control was most prominent at 100 ng/mL, while inhibition by tamoxifen was concentration dependent. IGF-1 was more effective in promoting growth in CP cell cultures with high IGF-1R expression, and it increased phosphorylation of Akt protein. Primary cell cultures can be established in more than 80% of fresh CP specimens. GH and its endogenous mediator, IGF-1, promotes CP cell growth in vitro, while tamoxifen inhibits growth.
authors.affiliation: Department of Neurosurgery, West China Hospital of Sichuan University, 37 Guoxue Road, Chengdu 610041, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Chao
authors.initials: C
authors.lastname: You
authors.forename: Liang
authors.initials: L
authors.lastname: Liu
authors.forename: Zhengxi
authors.initials: Z
authors.lastname: Rao
authors.forename: Xiutian
authors.initials: X
authors.lastname: Sima
authors.forename: Liangxue
authors.initials: L
authors.lastname: Zhou
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
mesh_terms: D000293:Adolescent; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002648:Child; D003397:Craniopharyngioma / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011986:Receptors, Somatotropin; D013629:Tamoxifen; D013006:Growth Hormone; D017526:Receptor, IGF Type 1; D051058:Oncogene Protein v-akt