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Titolo:
MUTATION AND EXPRESSION ANALYSIS OF THE P27 KIP1 GENE IN CORTICOTROPIN-SECRETING TUMORS/
Autore:
DAHIA PLM; AGUIAR RCT; HONEGGER J; FAHLBUSH R; JORDAN S; LOWE DG; LU X; CLAYTON R; BESSER GM; GROSSMAN AB;
Indirizzi:
ST BARTHOLOMEWS HOSP,DEPT ENDOCRINOL LONDON ENGLAND ST BARTHOLOMEWS HOSP,DEPT ENDOCRINOL LONDON ENGLAND ST BARTHOLOMEWS HOSP,DEPT PATHOL LONDON ENGLAND DANA FARBER CANC INST,DIV HEMATOL MALIGNANCIES BOSTON MA 02115 UNIV ERLANGEN NURNBERG,NEUROCHIRURG KLIN D-8520 ERLANGEN GERMANY ST MARYS HOSP,LUDWIG INST CANC RES LONDON ENGLAND UNIV KEELE,POSTGRAD MED SCH,DEPT MED STOKE ON TRENT STAFFS ENGLAND
Titolo Testata:
Oncogene
fascicolo: 1, volume: 16, anno: 1998,
pagine: 69 - 76
SICI:
0950-9232(1998)16:1<69:MAEAOT>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
DEPENDENT KINASE INHIBITOR; HUMAN PITUITARY-TUMORS; GROWTH-FACTOR-BETA; RETINOBLASTOMA GENE; P27(KIP1) GENE; CDK INHIBITOR; MICE LACKING; CELL-CYCLE; P27; G1;
Keywords:
CUSHINGS DISEASE; ACTH-TUMOR; P27-KIP1; MUTATION; CARCINOID; CELL CYCLE INHIBITOR; PITUITARY TUMOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
P.L.M. Dahia et al., "MUTATION AND EXPRESSION ANALYSIS OF THE P27 KIP1 GENE IN CORTICOTROPIN-SECRETING TUMORS/", Oncogene, 16(1), 1998, pp. 69-76

Abstract

The molecular mechanisms leading to Gushing's disease are unclear, Inhibitors of cyclin-cyclin dependent kinase (CDK) complexes are regulators of the cell cycle and may function as tumour suppressor genes, many of which have been involved in the pathogenesis of several human malignancies, A member of this family, the p27/kip1 gene, maps to chromosome 12p13 and encodes an inhibitor of several cyclin-CDK complexes; these control the progression of the cell cycle from G1 to S-phase, Complete lack of p27/kip1 function, as occurs in the p27/kip1 'knockout' mouse, produces a complex phenotype associated with the development of pituitary tumours, specifically those of the intermediate lobe corticotrophs, We therefore investigated whether structural and functional abnormalities of the p27/kip1 gene and loss at the chromosome 12p13 region were present in human corticotrophin (ACTH)-secreting pituitary tumours, We studied 21 pituitary tumours, of which 20 were ACTH-secreting(two of these had biochemical and histological features of 'intermediate-lobe' tumours and one was malignant) while the remaining tumour was a prolactinoma; three ectopic secretors of ACTH (two bronchial and one thymic carcinoid); and a non-secretory thymic carcinoid, The whole coding region of the p27/kip1 gene was screened for mutations by PGR-SSCP analysis and/or direct sequencing, while tumour mRNA expression was analysed by means of a semi-quantitative duplex PGR, Three polymorphic microsatellite markers of the 12p13 region were used to assess lossof heterozygosity (LOH) in 12 samples, Finally, tumour p27/kip1 protein expression was assessed by immunohistochemistry using a monoclonal antibody in 12 samples suitable for analysis, No sequence abnormalities were found in any of the samples other than a previously-described polymorphism, No LOH was observed in the tumours analysed, p27/kip1 mRNA expression was similar in tumour samples in comparison with normal pituitaries, Seven of the eight corticotroph tumours analysed by immunohistochemistry stained positive for p27/kip1, including the intermediate lobe, The only malignant pituitary tumour in the original series showed an absence of staining for p27/kip1, In addition, the three carcinoid tumours studied were negative on immunohistochemistry. Of a further three malignant pituitary tumours assessed, two (including a prolactinoma) were essentially negative, while the third was moderately positive, We conclude that mutations of the p27/kip1 gene, deletions of the 12p13 area or changes in expression, are not a general feature of corticotroph tumours, even those with intermediate lobe characteristics,However, other mechanisms of p27/kip1 inactivation, such as an abnormality at the post-translational level, may be related to more aggressive histological subtypes of ACTH-secreting and possibly other pituitary tumours.

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Documento generato il 01/12/20 alle ore 08:22:30