title: Silencing of HEPN1 is responsible for the aggressive biological behavior of pituitary somatotroph adenomas.
abstract: OBJECTIVE
  The pathogenic mechanisms underlying pituitary adenoma formation, progression, and invasion are poorly understood. To identify candidate tumor suppressor genes, we selected somatotroph adenomas as representative of pituitary adenomas.
  
  
  RESULTS
  We used genome-wide differential expression analysis in 15 invasive and 12 noninvasive somatotroph adenomas. HEPN1 reduction was more frequent in the invasive group, and this result was confirmed by qRT-PCR. To understand the function of HEPN1, the pituitary adenoma cell lines, GH3 and GT1.1, were stably transfected with short hairpin RNA (shRNA) targeting HEPN1 or ectogenic HEPN1 by lentivirus-mediated transfection. We found that HEPN1 overexpression in GH3 and GT1.1 cells inhibited cell proliferation, induced apoptosis, and attenuated invasive capacity, whereas HEPN1 silencing enhanced cell proliferation and invasion accompanied by decreased apoptosis. Western blot analysis revealed that HEPN1 overexpression decreased MMP-2, MMP-9, and Bcl-2 expression, but increased BAX, p53, and caspase-3 expression. In contrast, HEPN1 silencing increased MMP-2, MMP-9, and Bcl-2 expression, but decreased BAX, p53, and caspase-3 expression.
  
  
  CONCLUSIONS
  Taken together, our results suggest that reduction of HEPN1 may play an important role in the progression of pituitary somatotroph adenomas. HEPN1 may thus be a candidate as a prognostic predictor or an anticancer therapeutic target for patients with somatotroph adenoma.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Peng
authors.forename: Jingping
authors.initials: J
authors.lastname: Fan
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Juntian
authors.initials: J
authors.lastname: Lang
authors.forename: Junyu
authors.initials: J
authors.lastname: Wang
authors.forename: Huanhai
authors.initials: H
authors.lastname: Liu
authors.forename: Shuwei
authors.initials: S
authors.lastname: Zhao
authors.forename: Jianchun
authors.initials: J
authors.lastname: Liao
mesh_terms: D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C549604:HEPN1 protein, human; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9