title: PCTAIRE1/CDK16/PCTK1 is overexpressed in cutaneous squamous cell carcinoma and regulates p27 stability and cell cycle.
abstract: BACKGROUND
  PCTAIRE1 (also known as cyclin-dependent kinase 16 (Cdk16) and PCTK1) is a Cdk family protein that has been implicated in spermatogenesis. We recently revealed the function of PCTAIRE1 in the tumorigenesis of malignancies, including breast and prostate cancers; however, the tumorigenic function of PCTAIRE1 in cutaneous squamous cell carcinoma (SCC) remains unclear.
  
  
  OBJECTIVE
  In this study, we investigated the role of PCTAIRE1 in the tumorigenesis of cutaneous SCCs.
  
  
  RESULTS
  In cutaneous/oral SCC A431, DJM-1, HSC-3 cells, PCTAIRE1 gene-knockdown was found to diminish cell proliferation as assessed by cell counting and clonogenic assays. FACS analyses of annexin V-PI staining and DNA content showed PCTAIRE1 knockdown to cause G2/M arrest followed by apoptosis. The depletion of PCTAIRE1 was found to lead to the accumulation of tumor suppressor p27 and down-regulation of c-Myc. In tumor xenografts of A431 cells, the conditional knockdown of PCTAIRE1 restores p27 protein expression and suppresses tumor growth. Clinically, in primary tumors from patients with SCC, PCTAIRE1 is more highly expressed in malignant lesions than in adjacent normal epidermis. Conversely, expression levels of p27 are significantly lower in SCC than in normal epidermis.
  
  
  CONCLUSIONS
  Our findings reveal a crucial function for PCTAIRE1 in regulating p27, c-Myc levels and tumor growth in cutaneous SCC cells, suggesting that PCTAIRE1 could be a novel target for skin tumor treatment.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Japan. Electronic address: yanagi@med.hokudai.ac.jp.
authors.forename: Teruki
authors.initials: T
authors.lastname: Yanagi
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Hata
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Mizuno
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Kitamura
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Imafuku
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Nakazato
authors.affiliation: Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishihara
authors.affiliation: Department of Translational Pathology, Hokkaido University Graduate School of Medicine, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D049109:Cell Proliferation; D002469:Cell Separation; D002470:Cell Survival; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D015536:Down-Regulation; D004817:Epidermis / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*
chemical_list: C436291:CDKN1B protein, human; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases; C089463:PCTAIRE-1 protein kinase
keywords: Cell cycle; Cutaneous squamous cell carcinoma; Cyclin dependent kinase; p27