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Anticancer Res ; 40(1): 35-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892551


BACKGROUND/AIM: Co-expression of c-Met and ALDH1A3 indicates a poor prognosis in stage III-IV breast cancers and contributes to cell proliferation and tumor formation by ALDH1-positive breast CSCs. PKCλ is overexpressed and contributes to a poor prognosis in several cancers. MATERIALS AND METHODS: A breast cancer genomics data set (METABRIC, n=2509) was downloaded and analyzed, as was the effect c-Met and PKCλ inhibitors on ALDH1high cell viability and tumor-sphere formation. RESULTS: c-Met expression correlates with expression of PKCλ in breast cancer. Stage III-IV breast cancer patients with c-Methigh PKCλhigh ALDH1A3high have a poorer prognosis than patients with c-Metlow PKCλlow ALDH1A3low Foretinib and auranofin suppressed cell viability and tumor-sphere formation by ALDH1high cells. These results suggest that c-Met and PKCλ are cooperatively involved in cancer progression and contribute to poor prognoses in breast cancer. CONCLUSION: c-Met and PKCλ are potentially useful prognostic markers and therapeutic targets in late-stage breast cancer.

Aldeído Oxirredutases/genética , Biomarcadores Tumorais , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Proteína Quinase C/genética , Proteínas Proto-Oncogênicas c-met/genética , Aldeído Oxirredutases/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Proteína Quinase C/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo
Oncotarget ; 9(92): 36515-36529, 2018 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-30559934


Glyoxalase 1 (GLO1) is a ubiquitous enzyme involved in the detoxification of methylglyoxal, a cytotoxic byproduct of glycolysis that induces apoptosis. In this study, we found that GLO1 gene expression correlates with neoplasm histologic grade (χ 2 test, p = 0.002) and is elevated in human basal-like breast cancer tissues. Approximately 90% of basal-like cancers were grade 3 tumors highly expressing both GLO1 and the cancer stem cell marker ALDH1A3. ALDH1high cells derived from the MDA-MB 157 and MDA-MB 468 human basal-like breast cancer cell lines showed elevated GLO1 activity. GLO1 inhibition using TLSC702 suppressed ALDH1high cell viability as well as the formation of tumor-spheres by ALDH1high cells. GLO1 knockdown using specific siRNAs also suppressed ALDH1high cell viability, and both TLSC702 and GLO1 siRNA induced apoptosis in ALDH1high cells. These results suggest GLO1 is essential for the survival of ALDH1-positive breast cancer stem cells. We therefore conclude that GLO1 is a potential therapeutic target for treatment of basal-like breast cancers.