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Titolo:
The endogenous fibroblast growth factor-2 antisense gene product regulatespituitary cell growth and hormone production
Autore:
Asa, SL; Ramyar, L; Murphy, PR; Li, AW; Ezzat, S;
Indirizzi:
Mt Sinai Hosp, Dept Pathol & Lab Med, Toronto, ON M5G 2M9, Canada Mt SinaiHosp Toronto ON Canada M5G 2M9 Med, Toronto, ON M5G 2M9, Canada Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 2M9, Canada Univ Toronto Toronto ON Canada M5G 2M9 obiol, Toronto, ON M5G 2M9, Canada Dalhousie Univ, Dept Physiol & Biophys, Halifax, NS B3H 4H7, Canada Dalhousie Univ Halifax NS Canada B3H 4H7 hys, Halifax, NS B3H 4H7, Canada Mt Sinai Hosp, Dept Med, Toronto, ON M5G 2M9, Canada Mt Sinai Hosp Toronto ON Canada M5G 2M9 Med, Toronto, ON M5G 2M9, Canada
Titolo Testata:
MOLECULAR ENDOCRINOLOGY
fascicolo: 4, volume: 15, anno: 2001,
pagine: 589 - 599
SICI:
0888-8809(200104)15:4<589:TEFGFA>2.0.ZU;2-I
Fonte:
ISI
Lingua:
ENG
Soggetto:
MESSENGER-RNA; SUBCELLULAR-LOCALIZATION; NERVOUS-SYSTEM; PROLACTIN GENE; IN-VIVO; EXPRESSION; PROTEIN; TRANSCRIPTS; ADENOMAS; TUMOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Asa, SL Univ Hlth Network, Dept Pathol, Suite 4-302,610 Univ Ave, Toronto,ON M5G 2M9, Canada Univ Hlth Network Suite 4-302,610 Univ Ave Toronto ON Canada M5G 2M9
Citazione:
S.L. Asa et al., "The endogenous fibroblast growth factor-2 antisense gene product regulatespituitary cell growth and hormone production", MOL ENDOCR, 15(4), 2001, pp. 589-599

Abstract

Basic fibroblast growth factor (bFGF; FGF-2) is one of 19 related members of a growth factor family with mitogenic and hormone-regulatory functions. In Xenopus laevis oocytes, a 1.5-kb FGF-2 antisense (GFG) RNA complementaryto the third exon and 3'-untranslated region (UTR) of FGF-2 mRNA has been implicated in FGF-2 mRNA editing and stability. The human homolog has been cloned, and we localized this gene by yeast artificial chromosome (YAC), somatic cell, and radiation hybrid panels to the same chromosomal site as FGF-2 (chromosome 4, JO4513 adjacent to D4S430), confirming this as a human endogenous antisense gene. The full-length GFG antisense RNA encodes a 35-kDaprotein, which is highly homologous with the MutT family of antimutator nucleosidetriphosphatases (NTPases). We show that human pituitary tumors express FGF-P and its endogenous antisense partner GFG. While normal pituitary expresses GFG but not FGF-2, pituitary adenomas express FGF-2 and have reduced levels of GFG; aggressive and recurrent adenomas expressed more FGF than GFG mRNA. To examine the effects of this antisense gene in the pituitary,we transfected the pituitary-derived GH4 mammosomatotroph cell line with constructs encoding the full-length human GFG cDNA. Transiently and stably transfected cells expressed the 35-kDa GFG protein that was localized to thecytoplasm. These cells exhibited enhanced PRL expression as documented by transiently transfected PRL-luciferase reporter assay and by endogenous PRLprotein. GFG expression in these cells did not alter endogenous FGF-2 expression but increased the proportion of the higher molecular mass 22-kDa form of GH. Moreover, GFG expression inhibited cell proliferation as shown by [H-3]thymidine incorporation, proliferating cell nuclear antigen (PCNA) nuclear staining, and cell cycle analysis. We conclude that the GFG-encoded protein has divergent hormone-regulatory and antiproliferative actions in thepituitary that are independent of FGF-2 expression. GFG represents a novelmechanism involved in restraining pituitary tumor cell growth while promoting hormonal activity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 09:46:35