RESUMO
BACKGROUND: PTEN is a tumour suppressor protein with phosphatase activity frequently altered in several types of human cancers. MATERIALS AND METHODS: The PTEN effect was studied on the cell cycle (by bromdeoxyuridine incorporation) and on the phosphatidylinositol-3-kinase/protein kinase B/Akt (PI3-K/PKB/Akt) pathway regulating proteins (by immunocytochemical, Western blot analysis and kinase assay) upon transfection of wild-type PTEN and its mutant H123Y in breast cancer cell lines. RESULTS: The expression of the important proteins in the MCF-7 and BT-549 cells was characterised and the cellular localisation of PTEN was analysed. Transfection of H123Y led to the down-regulation of p27(Kip1) and p21(Waf1/Cip1) protein levels and the up-regulation of phosphorylated PKB/Akt. An overexpression of PTEN decreased cyclin E/cdk2 activity and inhibited S-phase entry in MCF-7. In BT-549 these changes were not observed, but overexpression of PTEN led to a diminution of PKB/Akt phosphorylation. CONCLUSION: PTEN function is mediated through the inhibition of the cell cycle and PKB/Akt phosphorylation in breast cancer cells.
Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias da Mama/enzimologia , Neoplasias da Mama/genética , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Ciclina D , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Inibidor de Quinase Dependente de Ciclina p27 , Ciclinas/biossíntese , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , PTEN Fosfo-Hidrolase/biossíntese , PTEN Fosfo-Hidrolase/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Fase S/fisiologia , TransfecçãoRESUMO
The majority of tumours in patients with hereditary non-polyposis colon cancer (HNPCC) occur in large intestine and endometrium; also, other tissues are at increased risk. We studied expression of hMLH1 and hMSH2 proteins in 148 normal samples of various tissues from non-HNPCC patients and in 14 normal colon tissues from HNPCC patients. Immunohistochemical technique was used. Intensity of nuclear staining, percentage of stained cells and H-scores were calculated. Tissues were divided into groups. Groups A, B and C included tissues with increased risk of cancer in HNPCC A) stomach, small and large bowel; (B) endometrium; (C) ovary, ureter, urinary bladder, kidney and liver. Group D tissues were without increased risk. Expression of the proteins was significantly higher in groups A, B and C compared with group D (P<0.0001, P=0.0004 for hMSH2 in C versus D). The expression was highest in testis. In colons of HNPCC patients, expression of the mutated gene product was significantly lower than in non-HNPCC patients. In conclusion, hMLH1/hMSH2 protein expression is constitutively higher in certain cell types of certain tissues, including the majority of tissues that are at increased risk of cancer in HNPCC. However, association of strong hMLH1/hMSH2 expression with cancer risk is not strictly valid.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Proteínas de Ligação a DNA/genética , Expressão Gênica , Predisposição Genética para Doença , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas/genética , Proteínas Adaptadoras de Transdução de Sinal , Pareamento Incorreto de Bases , Proteínas de Transporte , Reparo do DNA , Endométrio/química , Feminino , Humanos , Imuno-Histoquímica , Intestinos/química , Rim/química , Fígado/química , Masculino , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS , Proteínas Nucleares , Ovário/química , RNA Mensageiro/análise , Estômago/química , Ureter/química , Bexiga Urinária/químicaRESUMO
We report the clinical course of a 63-year-old man with a Warthin's tumour in the right parotid gland that had ulcerated the overlying skin. The ulceration may have been due to the malignant transformation of either the epithelial or lymphoid component or, as in very rare cases, it may have resulted from inflammatory alterations crossing the capsule of the tumour into the adjacent parotid parenchyma and surrounding skin. Only two similar cases of the latter have been reported to date. The main clinical pitfall of such an inflammatory skin disruption of an otherwise benign Warthin's tumour is that it may be mistaken for an infiltratively growing malignant lesion.
