title: GRP78 induced by estrogen plays a role in the chemosensitivity of endometrial cancer.
abstract: OBJECTIVE
  Molecular chaperone 78 kDa glucose-regulated protein (GRP78) is a residential protein in the endoplasmic reticulum (ER) that is induced by an unfolded-protein response triggered under many kinds of stress against a cell. GRP78 is also known to act as an anti-apoptotic factor by protecting ER-stress-induced cell death. In this study, we examined the significance of GRP78 expression in endometrial cancer.
  
  
  METHODS
  Tissue samples obtained from patients with a diagnosis of enodometrial cancer were subjected to immunohistochemistry and RT-PCR to determine protein and mRNA expression levels of GRP78 and estrogen receptor α. We used Western blot and RT-PCR to examine whether estrogen induced GRP78 expression in cancer cell lines. Western blots and MTT assays of GRP78 siRNA transfected Ishikawa and HHUA cells were used to demonstrate whether GRP78 is involved in chemoresistence.
  
  
  RESULTS
  GRP78 was highly expressed in well and moderately differentiated endometrial carcinoma. Estrogen induced GRP78 expression, which was correlated with cell viability and resistance to paclitaxel and cisplatin. Western blot analysis indicated that active caspase-3 and the 85-kDa protein poly (ADP-ribose) polymerase (PARP) were increased by incubation with either paclitaxel or cisplatin, suggesting that the apoptotic pathway was involved in cancer-drug-induced cell death.
  
  
  CONCLUSIONS
  These results may open up a novel therapeutic strategy for endometrial cancer: namely, the targeting of GRP78 to sensitize the tumor cell to chemotherapy.
authors.affiliation: Department of Obstetrics and Gynecology, Gunma University, 3-39-22 Showamachi Maebashi, Gunma 371‐8511, Japan
authors.forename: Baigalimaa
authors.initials: B
authors.lastname: Luvsandagva
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nakamura
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kitahara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoki
authors.forename: Tomomi
authors.initials: T
authors.lastname: Murata
authors.forename: Sadatomo
authors.initials: S
authors.lastname: Ikeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Minegishi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D000091342:Endoplasmic Reticulum Chaperone BiP; D047628:Estrogen Receptor alpha; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D004958:Estradiol; D017239:Paclitaxel; D002945:Cisplatin