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The role of the PTEN gene alterations in the pathogenesis of the endometrial carcinoma

Tomasz Kubiatowski1, Elżbieta Starosławska2, Jacek Wojcierowski1

Affiliacja i adres do korespondencji
GIN ONKOL, 2005, 3 (1), p. 40-46
Streszczenie

Sporadic endometrial carcinoma, most frequently diagnosed in routine practice, can be divided into two biologically and clinically distinctive subtypes of which one is estrogen-related (type I), the other estrogenunrelated (type II). The type I of endometrial carcinoma usually shows mutations of tumor suppressor phosphatase tensin homologue (PTEN) accompanied by K-Ras and β-catenin genes mutations and microsatellite instabilities whereas alternations of genes encoding p53 and p16 proteins or her2/neu amplifications are observed infrequently. Mutations of PTEN gene, localized on chromosome 10, leading to loss of gene function can increase the neoplastic transformation. PI3-k phosphorylation and accumulation of active forms of Akt within neoplastic cells lead to up-regulation of Bad protein resulting in Bcl-2, Bcl-xl proteins and caspase- 9 mediated apoptotic pathway inhibition. Heterogeneity of PTEN gene expression observed in surgical specimens correlates to histological stage of carcinoma and prognosis. PTEN expression is an important prognostic factor reflecting longer overall survival in group of patients diagnosed with advanced stages of endometrial cancer treated with adjuvant chemotherapy. Loss of PTEN gene expression can suggest tumor progression. However, incorporation of PTEN expression analysis into routine diagnostic procedure is limited by the presence of PTEN pseudogene, which is actively transcribed in various neoplastic tissues including endometrial cancer but not in normal endometrial tissue.

Słowa kluczowe
endometrial cancer, PTEN, mutations, carcinogenesis