BACKGROUND: Tuberin, the protein product of tuberous sclerosis gene 2 (TSC2), is the functional component of the TSC1/TSC2 complex and regulates cell cycle through activation of the cyclin-dependent kinase inhibitor p27. The transcriptional regulation of p27 is, however, also linked to a functional BRCA protein, since in BRCA1 mutant breast cancer cells, which lack the ability to repair DNA damages by homologous recombination, p27 is down-regulated. We have therefore investigated the expression of both tuberin and p27 in normal breast tissue, and in malignant epithelium from women with and without a BRCA mutation. MATERIALS AND METHODS: immunohistochemistry was used to compare p27 and tuberin protein expression in 26 BRCA1 and 2 mutation carriers, in 53 matched breast cancer patients without a family history, and in 74 benign breast tissues in a case-control study. RESULTS: Tuberin and p27 protein expression were significantly more common in benign when compared to malignant breast tissue (p = 0.01 and p = 0.03), but no difference was observed when sporadic and BRCA-mutated breast cancer specimen were compared. Tuberin and p27 were positively correlated with each other (p = 0.0017, r = 0.2527). Furthermore, p27 expression was positively correlated with ER and PR, and negatively correlated with tumor size. The expression of tuberin and p27 in breast cancer was not correlated with clinical outcome. CONCLUSION: Our results suggest that tuberin and p27 are aberrantly expressed in malignant tissue, but their expression does not appear to be dependent on the BRCA mutation state of a breast cancer patient.
BACKGROUND:Tuberin, the protein product of tuberous sclerosis gene 2 (TSC2), is the functional component of the TSC1/TSC2 complex and regulates cell cycle through activation of the cyclin-dependent kinase inhibitor p27. The transcriptional regulation of p27 is, however, also linked to a functional BRCA protein, since in BRCA1 mutant breast cancer cells, which lack the ability to repair DNA damages by homologous recombination, p27 is down-regulated. We have therefore investigated the expression of both tuberin and p27 in normal breast tissue, and in malignant epithelium from women with and without a BRCA mutation. MATERIALS AND METHODS: immunohistochemistry was used to compare p27 and tuberin protein expression in 26 BRCA1 and 2 mutation carriers, in 53 matched breast cancerpatients without a family history, and in 74 benign breast tissues in a case-control study. RESULTS:Tuberin and p27 protein expression were significantly more common in benign when compared to malignant breast tissue (p = 0.01 and p = 0.03), but no difference was observed when sporadic and BRCA-mutated breast cancer specimen were compared. Tuberin and p27 were positively correlated with each other (p = 0.0017, r = 0.2527). Furthermore, p27 expression was positively correlated with ER and PR, and negatively correlated with tumor size. The expression of tuberin and p27 in breast cancer was not correlated with clinical outcome. CONCLUSION: Our results suggest that tuberin and p27 are aberrantly expressed in malignant tissue, but their expression does not appear to be dependent on the BRCA mutation state of a breast cancerpatient.
Authors: P O Chappuis; L Kapusta; L R Bégin; N Wong; J S Brunet; S A Narod; J Slingerland; W D Foulkes Journal: J Clin Oncol Date: 2000-12-15 Impact factor: 44.544
Authors: V Esposito; A Baldi; A De Luca; A M Groger; M Loda; G G Giordano; M Caputi; F Baldi; M Pagano; A Giordano Journal: Cancer Res Date: 1997-08-15 Impact factor: 12.701
Authors: Fábia de Oliveira Andrade; Camile Castilho Fontelles; Mariana Papaléo Rosim; Tiago Franco de Oliveira; Ana Paula de Melo Loureiro; Jorge Mancini-Filho; Marcelo Macedo Rogero; Fernando Salvador Moreno; Sonia de Assis; Luiz Fernando Barbisan; Leena Hilakivi-Clarke; Thomas Prates Ong Journal: J Nutr Biochem Date: 2014-03-12 Impact factor: 6.048