title: Prospero homeobox 1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis.
abstract: BACKGROUND
  Prospero homeobox 1 (PROX1) functions as a tumor suppressor gene or an oncogene in various cancer types. However, the distinct function of PROX1 in gastric cancer is unclear. We determined whether PROX1 affected the oncogenic behavior of gastric cancer cells and investigated its prognostic value in patients with gastric cancer.
  
  
  METHODS
  A small interfering RNA against PROX1 was used to silence PROX1 expression in gastric cancer cell lines AGS and SNU638. Expression of PROX1 in gastric cancer tissues was investigated by performing immunohistochemistry. Apoptosis, proliferation, angiogenesis, and lymphangiogenesis were determined by performing the TUNEL assay and immunohistochemical staining for Ki-67, CD34, and D2-40.
  
  
  RESULTS
  PROX1 knockdown induced apoptosis by activating cleaved caspase-3, caspase-7, caspase-9, and poly(ADP-ribose) polymerase, and by decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. PROX1 knockdown also suppressed tumor cell proliferation. In addition, PROX1 knockdown decreased lymphatic endothelial cell invasion and tube formation and the expression of vascular endothelial growth factor (VEGF)-C and -D and cyclooxygenase (COX)-2. However, PROX1 knockdown only decreased umbilical vein endothelial cell invasion, not tube formation. The mean Ki-67 labeling index and lymphatic vessel density value of PROX1-positive tumors were significantly higher than those of PROX1-negative tumors. However, no significant difference was observed between PROX1 expression and apoptotic index or microvessel density. PROX1 expression was significantly associated with age, cell differentiation, lymph node metastasis, cancer stage, and poor survival.
  
  
  CONCLUSIONS
  These results indicate that PROX1 mediates the progression of gastric cancer by inducing tumor cell proliferation and lymphangiogenesis.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, 8 Hak-Dong, Dong-ku, Gwangju, 501-757, Republic of Korea.
authors.forename: Kang-Jin
authors.initials: KJ
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, 8 Hak-Dong, Dong-ku, Gwangju, 501-757, Republic of Korea.
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, 8 Hak-Dong, Dong-ku, Gwangju, 501-757, Republic of Korea.
authors.forename: Young-Lan
authors.initials: YL
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, 8 Hak-Dong, Dong-ku, Gwangju, 501-757, Republic of Korea.
authors.forename: Nuri
authors.initials: N
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, 8 Hak-Dong, Dong-ku, Gwangju, 501-757, Republic of Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, 8 Hak-Dong, Dong-ku, Gwangju, 501-757, Republic of Korea.
authors.forename: Dae-Seong
authors.initials: DS
authors.lastname: Myung
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, 8 Hak-Dong, Dong-ku, Gwangju, 501-757, Republic of Korea.
authors.forename: Wan-Sik
authors.initials: WS
authors.lastname: Lee
authors.affiliation: Department of Preventive Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Sun-Seog
authors.initials: SS
authors.lastname: Kweon
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, 8 Hak-Dong, Dong-ku, Gwangju, 501-757, Republic of Korea. yejoo@chonnam.ac.kr.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Joo
mesh_terms: D000230:Adenocarcinoma / Q000098:blood supply / Q000378:metabolism / Q000556:secondary*; D017209:Apoptosis; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein
keywords: Lymphangiogenesis; Prognosis; Proliferation; Prospero homeobox 1; Stomach neoplasm