title: Potential role of hematopoietic pre-B-cell leukemia transcription factor-interacting protein in oral carcinogenesis.
abstract: BACKGROUND
  Hematopoietic pre-B-cell leukemia transcription factor-interacting protein (HPIP) is a corepressor of pre-B-cell leukemia homeobox (PBX) 1 and is known to play a role in hematopoiesis. Recently, HPIP was demonstrated to promote breast cancer cell proliferation and hepatocellular carcinoma growth. Moreover, it has been revealed that homeobox and PBX proteins, the expression of which is regulated by HPIP, play key roles in cancer of various organs, including oral squamous cell carcinoma (OSCC). Nevertheless, there has not been any study regarding the role of HPIP in OSCC. This study investigated the expression of HPIP in normal oral mucosa, epithelial precursor lesion (OEPL), and OSCC, and the functional roles of HPIP in OSCC cells and normal keratinocytes.
  
  
  METHODS
  Immunohistochemical analysis of HPIP, Ki-67, and involucrin was performed in OSCC specimens, and the change in involucrin expression following RNA interference treatment against HPIP was examined by quantitative RT-PCR and Western blot analysis in SCC9 and NHEK cells undergoing extracellular calcium-induced differentiation. Matrigel transwell and cell proliferation assays for both cell lines transfected with HPIP siRNA were also conducted.
  
  
  RESULTS
  HPIP expression increased in OEPL and OSCC specimens. In vitro analysis revealed that HPIP suppressed differentiation and proliferation of SCC9 cells and transwell migration of NHEK cells, while HPIP promoted invasion of SCC9 and proliferation of NHEK cells. However, HPIP has no significant effect on NHEK cell differentiation.
  
  
  CONCLUSIONS
  HPIP may play a critical role in oral carcinogenesis and is thus a potential target for anticancer therapy, with particular emphasis on its involvement in differentiation and migration/metastasis.
authors: Division of Pathology, Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Shinagawa-ku, Tokyo, Japan.
authors: Seiji
authors: S
authors: Okada
authors: Tarou
authors: T
authors: Irié
authors: Junichi
authors: J
authors: Tanaka
authors: Rika
authors: R
authors: Yasuhara
authors: Gou
authors: G
authors: Yamamoto
authors: Tomohide
authors: T
authors: Isobe
authors: Chie
authors: C
authors: Hokazono
authors: Tetsuhiko
authors: T
authors: Tachikawa
authors: Yohko
authors: Y
authors: Kohno
authors: Kenji
authors: K
authors: Mishima
mesh_terms: D000328:Adult; D000368:Aged; D002118:Calcium / Q000494:pharmacology; D063646:Carcinogenesis / Q000473:pathology*; D002278:Carcinoma in Situ / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D056970:Co-Repressor Proteins; D005260:Female; D020868:Gene Silencing; D006801:Humans; D015603:Keratinocytes / Q000473:pathology; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009061:Mouth Mucosa / Q000473:pathology; D009062:Mouth Neoplasms / Q000473:pathology*; D011230:Precancerous Conditions / Q000473:pathology; D011498:Protein Precursors / Q000032:analysis; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis / Q000502:physiology*
chemical_list: D056970:Co-Repressor Proteins; D019394:Ki-67 Antigen; C413449:PBXIP1 protein, human; D011498:Protein Precursors; D034741:RNA, Small Interfering; D014157:Transcription Factors; C032253:involucrin; D002118:Calcium
keywords: carcinogenesis; differentiation; epithelial precursor lesion; hematopoietic pre-B-cell leukemia transcription factor-interacting protein; oral squamous cell carcinoma