Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Mutação , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteína Supressora de Tumor p53/genéticaRESUMO
BACKGROUND: Breast cancer is the most common cancer affecting women in the world today. Matrix metalloproteinases (MMPs) are a family of endopeptidases that can degrade extracellular matrix proteins and promote cell invasion and metastasis. MMPs are differentially expressed and their expressions are often associated with a poor prognosis for patients. OBJECTIVE: The aim of this study is to investigate and compare the expression of MMPs in different grades of human breast cancer tissues with normal breast tissues. PATIENTS AND METHODS: We collected 39 breast cancer samples (24 grade II and 15 grade III) along with 16 normal breast tissues from outside the tumor margin during cancer removal surgery. The samples were analysed for the expression of all known MMPs using real-time quantitative PCR. RESULTS: The results indicate that mRNA expressions of MMP-1, -9,-11,-15,-24 and -25 were upregulated in breast cancer tissues when compared to normal breast tissues. But, the mRNA expressions of MMP-10 and MMP-19 were downregulated in cancer tissue. In membrane associated MMPs like MMP-15 and MMP-24 we found a grade dependent increase of their mRNA expression. CONCLUSION: Our studies demonstrate that MMPs are differentially regulated in breast cancer tissues and they might play various roles in tumor invasion, metastasis and angiogenesis. Thus, MMPs are of immense value to be studied as diagnostic markers and drug target.
Assuntos
Neoplasias da Mama/enzimologia , Metaloproteinases da Matriz/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metaloproteinases da Matriz/genética , Pessoa de Meia-Idade , Transcrição GênicaRESUMO
Lithium, the lightest of all solid elements, has been used for the treatment of bipolar disorder since 1970s and prescribed to millions of women worldwide. Lithium chloride (LiCl) has been considered to be a potent inhibitor of glycogen synthase kinase-3ß (GSK-3ß), a serine/threonine kinase that is involved in the control of cell proliferation, differentiation, and apoptosis. In addition, GSK-3ß has been found to be inhibited endogenously by insulin-like growth factor-1 (IGF-1), a potent mitogen that plays an important role in the survival, growth, and differentiation of normal and neoplastic cells. Although both IGF-1 and LiCl have the ability to inhibit GSK-3ß, the specific signaling difference that mediates the survival of breast cancer cells was not clear. Therefore, in the present study, MCF-7 cells (human breast cancer cells) were treated with or without IGF-1 or LiCl in the presence or absence of LY294002 or PD98059 (pharmacological inhibitors) for 24h. As the expression of signaling proteins is crucial in the maintenance of cell survival and apoptosis, we analyzed the cells using immunoblotting procedure. In summary, our results have shown that LiCl and IGF-1 mediates cell survival by inhibiting GSK-3ß but differ in their mechanisms. IGF-1 involves PI3K/Akt or MAPK pathways whereas LiCl is completely independent of these pathways. IGF-1 upregulates anti-apoptotic proteins whereas LiCl downregulates apoptotic proteins in order to maintain cell survival.
