title: Progesterone Receptor Isoforms A and B in Pancreatic Neuroendocrine Tumor.
abstract: BACKGROUND
  Pancreatic neuroendocrine tumors (PNETs) have been reported to express progesterone receptor (PR), and its expression has been demonstrated to be a favorable prognostic factor in these patients. We examined the status of the PR isoforms PRA and PRB in the human PNET cell line and their association with cell proliferation of the tumor cells, which is closely related to the clinical outcome of PNET patients.
  
  
  METHODS
  Quantitative RT-PCR and cell proliferation assays were performed following treatment with progesterone and RU-486 as a PR antagonist in nontransfected and PRA-transfected cells of the NET cell line QGP-1, which expresses PRB in its native state. PRA, PRB and cyclin D1 (CCND1) were immunolocalized in 87 PNET cases, and the results were compared with clinicopathological parameters.
  
  
  RESULTS
  CCND1, c-Fos and c-Jun mRNA levels were all significantly increased by treatment with progesterone in QGP-1 cells with PRB expression compared with PRA-transfected cells (p = 0.02, p = 0.007 and p = 0.001, respectively). The proliferative activity of QGP-1 cells with PRB expression was also significantly stimulated by the administration of progesterone (p = 0.008). PRA immunoreactivity was significantly decreased in higher-grade PNETs (p = 0.04), whereas CCND1 was significantly elevated in higher-grade PNETs (p = 0.035).
  
  
  CONCLUSIONS
  The results of the present study demonstrate that PRA could play an inhibitory role in the cell proliferation of PNETs, possibly by inhibiting PRB-mediated signals in the presence of progesterone, which could result in decreased CCND1 expression. In addition, the status of PRA in tumor cells could be a prognostic factor in PNETs.
authors: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Samaneh
authors: S
authors: Yazdani
authors: Atsuko
authors: A
authors: Kasajima
authors: Hiroko
authors: H
authors: Ogata
authors: Saulo J A
authors: SJ
authors: Felizola
authors: Yasuhiro
authors: Y
authors: Nakamura
authors: Yoshiaki
authors: Y
authors: Onodera
authors: Mika
authors: M
authors: Watanabe
authors: Fuyuhiko
authors: F
authors: Motoi
authors: Michiaki
authors: M
authors: Unno
authors: Hironobu
authors: H
authors: Sasano
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015735:Mifepristone / Q000494:pharmacology; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000503:physiopathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D011374:Progesterone / Q000494:pharmacology; D020033:Protein Isoforms; D011980:Receptors, Progesterone / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D006727:Hormone Antagonists; D006728:Hormones; D020033:Protein Isoforms; D011980:Receptors, Progesterone; C101118:progesterone receptor A; C097314:progesterone receptor B; D015735:Mifepristone; D011374:Progesterone