title: Transcription factor-mediated proliferation and apoptosis in benign and malignant thyroid lesions.
abstract: Transcription factors play an essential role in regulating both cell proliferation and programmed cell death. Proliferation and apoptosis-related transcription factor immunoexpression patterns were concomitantly investigated in tissue sections of normal thyroid, goiters, follicular adenomas and well-differentiated papillary and follicular carcinomas using antibodies against prothymosin alpha, E2F-1, p53, Bcl2, and Bax proteins. Proliferation and apoptotic indices were determined by Ki-67 immunoreactivity and the terminal deoxynucleotidyl transferase-mediated deoxy uridine triphosphate nick-end labeling technique, respectively. Prothymosin alpha and E2F-1 immunoexpression levels were found to be significantly elevated in well-differentiated carcinomas compared to adenomas, goiters and normal tissues (P < 0.05). Both proteins were directly correlated with the proliferation index (P < 0.05). E2F-1 was additionally correlated with the apoptotic index (P < 0.05). The majority of cases were negative for p53 staining. Positive Bcl2 immunostaining was detected in all thyroid histotypes. None of the normal tissues showed Bax immunoreactivity, while positive accumulation differed significantly between hyperplastic and neoplastic histotypes. Direct correlations were observed between prothymosin alpha and Bcl2 as well as between E2F-1 and Bax immunoexpression (P < 0.05). These data demonstrate that prothymosin alpha and E2F-1 are strongly involved in the proliferation processes of thyroid neoplasias. Furthermore, prothymosin alpha may promote cell survival through the Bcl2 anti-apoptotic pathway, while E2F-1-induced apoptosis via p53-independent pathways may be associated with transcriptional activation of bax pro-apoptotic gene.
authors.affiliation: Second Department of Cardiology, Evangelismos General Hospital of Athens, Greece. k.letsas@mail.gr
authors.forename: Konstantinos P
authors.initials: KP
authors.lastname: Letsas
authors.forename: Maria
authors.initials: M
authors.lastname: Frangou-Lazaridis
authors.forename: Angelos
authors.initials: A
authors.lastname: Skyrlas
authors.forename: Agathocles
authors.initials: A
authors.lastname: Tsatsoulis
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Malamou-Mitsi
mesh_terms: D000236:Adenoma / Q000473:pathology / Q000503:physiopathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D018265:Carcinoma, Papillary, Follicular / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000032:analysis / Q000276:immunology / Q000502:physiology; D050687:E2F1 Transcription Factor / Q000032:analysis / Q000276:immunology / Q000502:physiology; D005260:Female; D006042:Goiter / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000032:analysis / Q000276:immunology / Q000502:physiology; D012097:Repressor Proteins / Q000032:analysis / Q000276:immunology / Q000502:physiology; D013947:Thymosin / Q000031:analogs & derivatives / Q000032:analysis / Q000276:immunology / Q000502:physiology; D013959:Thyroid Diseases / Q000473:pathology* / Q000503:physiopathology; D013961:Thyroid Gland / Q000737:chemistry / Q000166:cytology / Q000473:pathology*; D013964:Thyroid Neoplasms / Q000473:pathology* / Q000503:physiopathology; D014157:Transcription Factors / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000276:immunology / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000276:immunology / Q000502:physiology; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000276:immunology / Q000502:physiology
chemical_list: C119386:BCLAF1 protein, human; D004268:DNA-Binding Proteins; D050687:E2F1 Transcription Factor; D011498:Protein Precursors; D012097:Repressor Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; C040782:prothymosin alpha; D013947:Thymosin