RESUMO
BACKGROUND: Lamin A/C alternative splice variants (Lamin A, Lamin C, Lamin AΔ10 and Lamin AΔ50) have been implicated in cell cycle regulation, DNA replication, transcription regulation, cellular differentiation, apoptosis and aging. In addition, loss of Lamin A/C expression has been observed in several cancers, including breast cancer, and it has been found that Lamin A/C suppression may lead to cancer-like aberrations in nuclear morphology and aneuploidy. Based on these observations, we hypothesized that Lamin A/C transcript variant quantification might be employed for the diagnosis of breast cancer. METHODS: Newly designed TaqMan qRT-PCR assays for the analysis of Lamin A/C splice variants were validated and their use as biomarkers for the diagnosis of breast cancer was assessed using 16 normal breast tissues and 128 breast adenocarcinomas. In addition, the expression levels of the Lamin A/C transcript variants were measured in samples derived from seven other types of cancer. RESULTS: We found that the expression level of Lamin C was significantly increased in the breast tumors tested, whereas the expression levels of Lamin A and Lamin AΔ50 were significantly decreased. No significant change in Lamin AΔ10 expression was observed. Our data also indicated that the Lamin C : Lamin A mRNA ratio was increased in all clinical stages of breast cancer. Additionally, we observed increased Lamin C : Lamin A mRNA ratios in liver, lung and thyroid carcinomas and in colon, ovary and prostate adenocarcinomas. CONCLUSIONS: From our data we conclude that the Lamin C : Lamin A mRNA ratio is increased in breast cancer and that this mRNA ratio may be of diagnostic use in all clinical stages of breast cancer and, possibly, also in liver, lung, thyroid, colon, ovary and prostate cancers.
Assuntos
Processamento Alternativo/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Lamina Tipo A/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Lamina Tipo A/metabolismo , Especificidade de Órgãos/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: The mature human insulin receptor (INSR) has two isoforms: The A isoform and the B isoform. INSR upregulation has been suggested to play a role in cancer. OBJECTIVE: To establish quantitative PCR method for INSR transcript variants and examine their differential expression as a diagnostic tumor marker in breast cancer. METHODS: The differential expression of IR-A and IR-B were evaluated by TaqMan qRT-PCR assay in the commercially available Breast Cancer Disease cDNA and Cancer Survey cDNA arrays. RESULTS: The mRNA expression levels of IR-A was statistically significantly higher in breast cancer when compared to normal breast tissue while IR-B mRNA expression was down regulated significantly in breast cancer. Stratification of patients into groups according to metastatic stages indicated statistically significantly higher levels of IR-A mRNA in clinical stage (CS)-IV, and lower IR-B levels in CS-IIA, CS-IIIB and CS-IIIC. However, IR-A:IR-B ratio showed a statistically significant increase in all stages. Cancer Survey cDNA array demonstrated lower levels of IR-B mRNA in breast adenocarcinoma, liver carcinoma and lung carcinoma only while IR-A expression was significantly altered in kidney carcinoma without any significant differences in IR-A:IR-B ratios. CONCLUSIONS: The results demonstrate an increased IR-A:IR-B ratio in all clinical stages of breast cancer. Thus, IR-A:IR-B ratio may have a diagnostic biomarker utility in breast cancer.
Assuntos
Antígenos CD/biossíntese , Biomarcadores Tumorais/biossíntese , Neoplasias da Mama/genética , Isoformas de Proteínas/biossíntese , Receptor de Insulina/biossíntese , Antígenos CD/genética , Biomarcadores Tumorais/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estadiamento de Neoplasias , Isoformas de Proteínas/genética , RNA Mensageiro , Receptor de Insulina/genéticaRESUMO
BACKGROUND: To evaluate sirtuin-7 (SirT7) mRNA expression status in breast cancer patients with different metastatic stages and survey SirT7 mRNA expression status in eight different types of cancer. METHODS: The expression of SirT7 in the commercially available TissueScan qPCR Breast Cancer Disease cDNA arrays containing 16 normal, 23 Stage I, 36 IIA, 22 IIB, 8 IIIA, 23 IIIA, 6 IIIB, 13 IIIC, and 5 IV were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Similar analysis was performed in TissueScan qPCR Cancer Survey cDNA array, which includes breast, colon, kidney, liver, lung, ovarian, prostate, and thyroid specimens. RESULTS: The mRNA expression levels of SirT7 were significantly higher in breast cancer samples compared to normal breast specimens (P < 0.001). Stratification of patients into groups according to metastatic stages indicated statistically significantly higher levels of SirT7 mRNA in CS-I, CS-II, and CS-III when compared to normal breast tissue (P < 0.05). Notably, SirT7 mRNA levels were higher in CS-I, CS-IIA, CS-IIB, and CS-IIIA (P < 0.05). Additionally, there were significantly lower SirT7 mRNA levels in thyroid carcinoma when compared to their corresponding normal tissue (P < 0.05). CONCLUSIONS: Our results indicate an increase in the mRNA expression level of SirT7 in breast cancer, particularly in CS-I, CS-IIA, CS-IIB, and CS-IIIA. The relationship of altered SirT7 with breast cancer progression and patient survival should be prospectively explored in future studies.