title: Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma.
abstract: Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed MGC and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty diagnosed BCC cases were collected to determine the telomere length, the presence of senescent cells, and the expression levels of the telomere capping shelterin complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the shelterin subunits, shortened telomere length, over-expressed Ki-67, and Bcl2 as well as mutations in P53 were detected both in MGC and BCC. It suggests that the decreased protein levels of the shelterin complex and the shortened telomere length contribute to the tumorigenesis of MGC and BCC. However, several parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly mutated in MGC; (iii) Siah1 mRNA was over-expressed in BCC; (iv) BCC samples contain a higher level of senescent cells; (v) Ki-67 and Bcl2 expression were lower in BCC. These results support a model where a preserved P53 checkpoint in BCC leads to cellular senescence and reduced tumor proliferation as compared to MGC.
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Emergency, International laboratory in Hematology and Cancer (LIA), 'Pôle sino-français de recherche en sciences du vivant et génomique', Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Shengfang
authors.initials: S
authors.lastname: Ge
authors.affiliation: Department of Emergency, International laboratory in Hematology and Cancer (LIA), 'Pôle sino-français de recherche en sciences du vivant et génomique', Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.|Institute for Research on Cancer and Aging, Nice (IRCAN), Nice University, CNRS UMR7284/INSERM U1081, Faculty of Medicine, Nice, France.|Medical Genetic Unit, CHU Nice, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Gilson
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Renbing
authors.initials: R
authors.lastname: Jia
authors.affiliation: Department of Emergency, International laboratory in Hematology and Cancer (LIA), 'Pôle sino-français de recherche en sciences du vivant et génomique', Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Xianqun
authors.initials: X
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002280:Basal Cell Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D016922:Cellular Senescence / Q000235:genetics*; D005142:Eyelid Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000098563:Seven in Absentia Proteins
chemical_list: D009687:Nuclear Proteins; D021122:Protein Subunits; D012333:RNA, Messenger; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D016159:Tumor Suppressor Protein p53; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
keywords: P53; Siah1; basal cell carcinoma; meibomian gland carcinoma; senescence; shelterin complex