RESUMO
The Cyclin D1 protein has been extensively studied over the last decades, for its various roles in physiological processes, both in normal and cancer cells. Gene amplifications and overexpression of CCND1 are frequently reported in several types of cancers, including breast carcinomas, showing the increasing relevance of Cyclin D1 in tumorigenesis. Little is known about the role of this protein in the metastatic process, and the main objective of this study was to evaluate the importance of the CCND1 as a potential marker of tumor progression in breast carcinomas, in a sample collected in Southern Brazil. We studied 41 samples of formalin-fixed paraffin-embedded tissue sections from invasive ductal breast carcinomas subdivided into metastatic (n = 19) and non-metastatic (n = 22) tumors. Gene expression analysis was performed through Quantitative Real-Time PCR and immunohistochemistry. In spite of the higher expression levels of CCND1 mRNA and protein in tumors when compared with the control samples, no differences were observed between the metastatic and non-metastatic groups, suggesting that, in these samples, the expression of CCND1 has no significant influence on the metastatic process. Further studies must be performed in an attempt to clarify the diagnostic and prognostic value of Cyclin D1 in breast cancers, as well as the mechanisms that trigger its overexpression in tumors.
Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Ciclina D1/genética , Ciclina D1/metabolismo , Expressão Gênica , Adulto , Idoso , Brasil , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Pessoa de Meia-Idade , PrognósticoRESUMO
CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A->G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A->G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95% CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95% CI = 0.70-2.79) with OSCC.
Assuntos
Citocromo P-450 CYP1A1/genética , Glutationa S-Transferase pi/genética , Neoplasias Bucais/genética , Neoplasias de Células Escamosas/genética , Polimorfismo Genético/genética , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Marcadores Genéticos/genética , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/enzimologia , Neoplasias de Células Escamosas/enzimologia , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
CYP1A1 and GSTP1 polymorphisms have been associated with a higher risk to develop several cancers, including oral squamous cell carcinoma (OSCC), which is closely related to tobacco and alcohol consumption. Both genes code for enzymes that have an important role in activating or detoxifying carcinogenic elements found in tobacco and other compounds, and polymorphic variants of these genes may result in alterations of the enzymatic activity. The CYP1A1 gene codes for the enzyme aryl hydrocarbon hydroxylase, which is responsible for the metabolism of polycyclic aromatic hydrocarbons. The investigated polymorphism, Ile/Val, seems to increase the activity of the enzyme in homozygous individuals, leading to an accumulation of carcinogens. The Ile/Val polymorphism occurs because of an A->G transition at exon 7, resulting in the CYP1A1*2B allele. The GSTP1*B variant shows an A->G transition at exon 5, changing the amino acid Ile to Val, with a reduced catalytic activity of the enzyme. Due to this reduction, the carriers of mutant alleles lost the capability to metabolize carcinogens, which could be responsible for a higher susceptibility to cancer. We conducted a case-control study in a group of 72 cases with newly diagnosed OSCC and 60 healthy controls matched for age, gender, smoking habits, and ethnicity. We used PCR methods to identify the allelic variants CYP1A1*2B and GSTP1*B. The data obtained showed no statistically significant association of allelic or genotypic variants of CYP1A1*2B (OR = 1.06; 95 percent CI = 0.49-2.29) and GSTP1*B (OR = 1.40; 95 percent CI = 0.70-2.79) with OSCC.