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Involvement of ER-α36 in the malignant growth of gastric carcinoma cells is associated with GRP94 overexpression.

AbstractAIMS:
This study aimed to examine the involvement of glucose-regulated protein 94 (GRP94) in oestrogen receptor-α36 (ER-α36)-mediated oestrogen signalling in gastric cancer development.
METHODS AND RESULTS:
A total of 130 formalin-fixed and paraffin-embedded gastric tumour samples with corresponding normal gastric and tumour-adjacent tissues were used. High levels of GRP94 expression (2+ or 3+) were observed in 109 of 130 gastric carcinomas (83.85%) by immunohistochemistry, and in 13 of 18 tumour specimens (72.22%) with Western blot analysis. GRP94 expression was correlated positively with gender, tumour stage, lymph node metastasis and ER-α36 expression (P < 0.05). Oestrogen treatment up-regulated both GRP94 and ER-α36 expression in gastric cancer SGC7901 cells. In addition, steady state levels of GRP94 protein were decreased in established gastric cancer SGC7901 cells with knocked-down levels of ER-α36 expression and in xenograft tumours formed by these cells. Forced expression of recombinant ER-α36 in SGC7901 cells, however, up-regulated the levels of GRP94 expression.
CONCLUSIONS:
Glucose-regulated protein 94 is a downstream effector of ER-α36-mediated oestrogen signalling, and may be involved in ER-α36 function during gastric carcinogenesis.
AuthorsZhengqi Fu, Hao Deng, Xuming Wang, Xiuping Yang, Zhaoyi Wang, Lijiang Liu
JournalHistopathology (Histopathology) Vol. 63 Issue 3 Pg. 325-33 (Sep 2013) ISSN: 1365-2559 [Electronic] England
PMID23829397 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 John Wiley & Sons Ltd.
Chemical References
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Membrane Glycoproteins
  • endoplasmin
Topics
  • Adenocarcinoma (etiology, metabolism, pathology)
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Blotting, Western
  • Carcinogenesis
  • Cell Line, Tumor
  • Estrogen Receptor alpha (antagonists & inhibitors, genetics, metabolism)
  • Female
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Immunohistochemistry
  • Lymphatic Metastasis
  • Male
  • Membrane Glycoproteins (metabolism)
  • Mice
  • Mice, Nude
  • Middle Aged
  • Neoplasm Staging
  • Signal Transduction
  • Stomach Neoplasms (etiology, metabolism, pathology)
  • Up-Regulation

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