Abnormalities in the NF-κB family and related proteins in endometrial carcinoma
Martínez-Guitarte, Jose Luis
Dolcet Roca, Xavier
Llobet Navàs, David
MetadataShow full item record
The NF-κB family of transcription factors regulates a wide variety of cellular processes including cell growth, differentiation, and apoptosis. A tissue microarray was constructed from paraffin wax-embedded blocks from 95 endometrial carcinomas (EC), previously studied for microsatellite instability, as well as for alterations in PTEN, k-RAS and betacatenin. Immunohistochemical evaluation included members of the NF-κB (p50, p65, p52, c-Rel, Rel-B) and the IκB (IκBα, IκBβ, IκBε, Bcl-3) families, as well as putative targets of NF-κB such as Flip, Bcl-xL, Cyclin D1, and oestrogen and progesterone receptors. Results were correlated with the clinical and pathological data. Nuclear immunostaining for members of the NF-κB family was frequent in EC (p50, 20%; p65, 16.5–21.9%; p52, 9.3%; cRel, 48.9%; Rel-B, 15.7%); and it correlated with negativity for members of the IκB family in some cases. There was a statistically significant association between immunoreaction for p50 and p65 (p = 0.006), suggesting activation of the so-called ‘classic form’ of NF-κB, similar to that described in breast cancer. Bcl-3 nuclear immunostaining was detected in 60.7% of cases. The vast majority of p52-positive tumours showed Bcl-3 nuclear immunoreaction (p = 0.038). Immunostaining for putative targets of NF-κB was as follows: Bcl-xL, 76.2% (p = 0.001); Flip 43.0%; Cyclin D1, 64.79%. p65 immunostaining correlated with increased immunoreaction for steroid hormone receptors. No correlation was found between NF-κB nuclear pattern and the presence of microsatellite instability, or alterations in PTEN, kRAS, or beta-catenin. These results suggest that the NF-κB and IκB families of genes may be important in endometrial carcinogenesis, by controlling apoptosis and cell proliferation.
Is part ofJournal of Pathology, 2004, vol. 204, núm. 5, p. 569-577
European research projects
Showing items related by title, author, creator and subject.
Immunohistochemical analysis of PTEN in endometrial carcinoma: a tissue microarray study with a comparison of four commercial antibodies in correlation with molecular abnormalities Pallares, Judit; Bussaglia, Elena; Martínez-Guitarte, Jose Luis; Dolcet Roca, Xavier; Llobet Navàs, David; Rué i Monné, Montserrat; Sanchez-Verde, Lidia; Palacios, José; Prat, Jaime; Matias-Guiu, Xavier (Nature Publishing Group, 2005)The tumor suppressor gene PTEN/MMAC1 is located on chromosome 10q23.3. Inactivation of PTEN, either by mutations, deletions, or promoter hypermethylation, has been identified in a wide variety of tumors. Inactivation of ...
FLIP is frequently expressed in endometrial carcinoma and has a role in resistance to TRAIL-induced apoptosis Dolcet Roca, Xavier; Llobet Navàs, David; Pallares, Judit; Rué i Monné, Montserrat; Comella i Carnicé, Joan Xavier; Matias-Guiu, Xavier (Nature Publishing Group, 2005)The FLICE-inhibitory protein (FLIP) plays a key role in the regulation of apoptosis triggered by death ligands. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been shown to induce apoptosis in some types ...
KSR1 is overexpressed in endometrial carcinoma and regulates proliferation and TRAIL-induced apoptosis by modulating FLIP levels Llobet Navàs, David; Eritja Sánchez, Núria; Domingo, Mónica; Bergadà Bertran, Laura; Mirantes Barbeito, Cristina; Santacana Espasa, Maria; Pallares, Judit; Macià Armengol, Anna; Yeramian Hakim, Andree; Encinas Martín, Mario; Moreno-Bueno, Gema; Palacios, José; Lewis, Robert E.; Matias-Guiu, Xavier; Dolcet Roca, Xavier (Elsevier Inc, 2011)The Raf/MEK/extracellular signal-regulated kinase (ERK) pathway participates in many processes altered in development and progression of cancer in human beings such as proliferation, transformation, differentiation, and ...