http___medlib.mef.hr_567__1.xml
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Pavelić, Krešimir and Dedivitis, Rogerio A. and Kapitanović, Sanja and Čačev, Tamara and Guirado, Cristiano R. and Danić, Davor and Radošević, Senka and Brkić, Kornelije and Pegan, Boris and Križanac, Šimun and Kusić, Zvonko and Spaventi, Šime and Bura, Miljenko (2006) Molecular genetic alterations of FHIT and p53 genes in benign and malignant thyroid gland lesions. Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 599 (1-2). Abstract Several oncogenes and tumor-suppressor genes are involved either as early or late event in thyroid gland carcinogenesis. Human FHIT (fragile histidine triad) gene is highly conserved gene whose loss of function may be important in the development and/or progression of various types of cancer. We undertook this study to analyze FHIT and p53 gene status in different benignant and malignant thyroid tumors. Status of these genes as well as intensity of apoptosis was analyzed in tumor tissues by molecular genetic methods, immunohistochemistry, and FACS-scan analysis. The majority of the malignant thyroid cancers displayed aberrant expression of FHIT gene, concominant with p53 gene inactivation. This is followed by low rate of apoptosis, which may be important in the development and/or progression of thyroid cancer. We found higher incidence of p53 mutation and aberrant processing of FHIT mRNA in malignant tumors (papillary, follicular, medullary and anaplastic carcinomas) and i! n those tumors with distant metastasis. The growth of p53(-)/FHIT- follicular carcinoma of human origin was much faster in nude mice than p53(+)/FHIT- follicular carcinoma, and mice had shorter survival rate. Our results show a correlation between aberrant FHIT and p53 expression, low rate of apoptosis, and malignancy. Concomitant aberration of FHIT gene and p53 could be responsible for development of highly malignant types of thyroid cancer and may be considered as a prognostic marker for these tumors. Actions (login required) Downloads Downloads per month over past year
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Lončar, Božo (2008) Poremećaj funkcije gena FHIT u karcinomima debelog i završnog crijeva. PhD thesis, Sveučilište u Zagrebu. Croatian abstract Karcinom debelog crijeva jedan je od najčešćih zloćudnih tumora i drugi po redu uzrok smrti od raka u razvijenim zemljama. Većina karcinoma debelog crijeva posljedica je stupnjevitog procesa tijekom kojeg iz dobroćudnog adenoma kao posljedica naslijeđenih i/ili stečenih mutacija nastaje zloćudni invazivni tumor. Gen FHIT (od engl. Fragile Histidine Triad), tumor supresorski gen smješten je na kromosomu 3 u čovjeka (3p14.2) i promijenjen je u različitim tumorima čovjeka uključujući i tumore probavnog sustava. Cilj našeg istraživanja bio je ispitati gubitak heterozigotnosti te ekspresiju gena FHIT na razini specifične mRNA i proteina u sporadičnim karcinomima kolona. Rezultati naših istraživanja su pokazali su da je gubitak heterozigotnosti gena FHIT prisutan u 19,2% sporadičnih karcinoma kolona. Razina ekspresije gena FHIT u tumorima bila je statistički značajno niža u odnosu na ekspresiju u pripadajućoj normalnoj sluznici (p 0,00002). U našem je istraživanju najveći broj uzoraka sporadičnih karcinoma kolona bio negativan na prisustvo proteina FHIT (51,7%). Naši rezultati pokazuju jasnu korelaciju između gubitka heterozigotnosti te smanjene ekspresije gena FHIT na razini specifične mRNA kao i proteina s napredovanjem i metastaziranjem sporadičnih karcinoma kolona. Smanjena ili potpuno ugašena ekspresija proteina FHIT mogla bi biti prognostički biljeg za sporadične karcinome kolona s tim da bi postojeće rezultate trebalo proširiti na veći broj uzoraka te analizu preživljenja. English abstract Colorectal adenocarcinoma is one of the most common cancers and the second leading cause of death in the Western world. This disease arises from the accumulation of mutations in oncogenes and tumor-suppressor genes during progression from normal epithelium to adenoma and malignant invasive carcinoma. Fragile histidine triad (FHIT) gene, a candidate tumor suppressor gene located at 3p14.2, has been shown to be involved in carcinogenesis of many human tumors, including digestive tract tumors. The main goal of this study was to investigate genetic changes in FHIT gene in order to elucidate the mechanisms of its role in development and progression of sporadic colon cancer. Loss of heterozygosity (LOH) of FHIT gene was positive in 19,2% of sporadic colon cancers. FHIT gene mRNA expression in tumor cells was statistically significant decreased in comparison to adjacent normal mucous tissue (p 0.00002). The most of sporadic colon tumor specimens were negative for FHIT protein expression (51,7%). We showed that positive LOH, decreased mRNA and protein expression of FHIT gene significantly correlate with the progression of sporadic colon cancer, with tumor size, differentiation and Dukes’ stage. The results of this study could be used in the future for more efficient surveillance of the patients with sporadic colon cancer. Actions (login required)