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Pregled bibliografske jedinice broj: 196138

Molecular genetics of malignant insulinoma


Pavelić, Krešimir; Hrašćan, Reno; Kapitanović, Sanja; Vraneš, Z.; Čabrijan, Tomislav; Spaventi, Šime; Koršić, Mirko; Križanac, Šimun; Li, Y.Q.; Stambrook, Peter et al.
Molecular genetics of malignant insulinoma // Anticancer research, 16 (1996), 4A; 1707-1717 (međunarodna recenzija, članak, znanstveni)


Naslov
Molecular genetics of malignant insulinoma

Autori
Pavelić, Krešimir ; Hrašćan, Reno ; Kapitanović, Sanja ; Vraneš, Z. ; Čabrijan, Tomislav ; Spaventi, Šime ; Koršić, Mirko ; Križanac, Šimun ; Li, Y.Q. ; Stambrook, Peter ; Gluckman, J.L. ; Pavelić, Zlatko

Izvornik
Anticancer research (0250-7005) 16 (1996), 4A; 1707-1717

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Genetics ; malignant insulinomas
(Genetics ; imalignant nsulinomas)

Sažetak
Malignant insulinoma is an rare form of cancer with poor prognosis and a reported 5-year survival of 35%. Relatively little is known about the etiology of this disease or of the oncogenes and tumor suppressor genes that participate in its genesis and progression. To address this issue, several protooncogenes, including K-ras, N-ras, erb-2, erb-3, c-myc, c-fos, c-jun were examined. Also analyzed was the expression of the growth factors TGF-alpha, EGF, and insulin as well as the EGF receptor (EGF-R), p53 and the putative anti-metastasis gene nm23-H1. These were examined in malignant insulinomas, benign insulinomas, pancreatic B cell hyperplasias and in normal endocrine pancreas. Normal endocrine pancreas showed moderate immunoreaction for c-myc and a strong reaction for insulin. All other parameters were negative. Benign pancreatic B cell hyperplasias were slightly or moderately positive for N-ras and TGF-alpha, and were weakly positive for EGF-R. They were strongly positive for c-myc and insulin. In malignant insulinomas there was strong immunoreaction for c-myc, TGF-alpha, N-ras, K-ras and p53. Insulin reaction was moderate or strong. Molecular genetic studies have been performed for the presence of activating point mutations in codon 12 of the c-K-ras oncogene. Mutations were detected using primer-mediated, mutant-enriched, polymerase chain reaction - restriction fragment length polymorphism analysis and were further characterized by allele-specific oligonucleotide hybridization. Four out of six patients with malignant insulinoma and two out of eight patients with benign insulinoma harbored K-ras point mutations at codon 12. All patients with mutated K-ras oncogene also had elevated levels of p53 protein as well as c-myc and TGF-alpha. In one extremely malignant case we found concomitant mutation at condon 12 of K-ras and codon 61 of the N-ras gene. Our data were consistent with the idea that malignant progression is accompanied by the progressive accumulation of multiple genetic lesions and suggest that activation of myc, TGF-alpha and ras genes may be early events in the development of insulinoma.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti



POVEZANOST RADA


Ustanove
Institut "Ruđer Bošković", Zagreb,
KBC "Sestre Milosrdnice",
Klinički bolnički centar Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE