Progesterone Induces NFκB DNA Binding Activity through a PI3K/Akt-Dependent Pathway in MCF-7 Breast Cancer Cells
Fernando Candanedo-Gonzalez,
Octavio Galindo-Hernandez,
Nathalia Serna-Marquez,
Roberto Espinosa-Neira,
Adriana Soto-Guzman,
Pedro Cortes-Reynosa,
Eduardo Perez Salazar
Issue:
Volume 2, Issue 4, July 2014
Pages:
63-69
Received:
13 June 2014
Accepted:
28 June 2014
Published:
10 July 2014
Abstract: Progesterone (PG) is a steroid hormone that regulates normal reproductive functions including uterine and mammary gland development. The PG receptor belongs to the nuclear receptor superfamily of ligand dependent transcription factors that mediates gene expression, however, it also promotes cell signaling pathways through a non-genomic pathway including the activation of PI3K/Akt and Src/ERK1/2 pathways. However the role of PG in NFκB-DNA complex formation remains to be studied. We demonstrate here that PG induces Akt2 activation and an increase of NFκB DNA binding activity in MCF-7 breast cancer cells. Akt2 activation requires PI3K activity, whereas increase of NFκB DNA binding activity requires PI3K, mTOR, Akt, Src, and G-proteins activity, as well as the integrity of cytoskeleton. In summary, our findings demonstrate that PG induces an increase of NFκB DNA binding activity in MCF-7 cells.
Abstract: Progesterone (PG) is a steroid hormone that regulates normal reproductive functions including uterine and mammary gland development. The PG receptor belongs to the nuclear receptor superfamily of ligand dependent transcription factors that mediates gene expression, however, it also promotes cell signaling pathways through a non-genomic pathway incl...
Show More
Correlation of Oncologic Long-Term Results and Genetic Instability in Soft Tissue Sarcomas
Reiner Wirbel,
Steffen Weber,
Joachim Hans,
Wolf Mutschler
Issue:
Volume 2, Issue 4, July 2014
Pages:
74-81
Received:
18 June 2014
Accepted:
4 July 2014
Published:
20 July 2014
Abstract: Purpose: Soft tissue sarcomas (STS) represent a heterotop group of tumours. Microsatellite instabilities (MSI) and loss of heterozygosity (LOH) as phenomena of a genetic instability should be analysed in STS and correlated with the long-term oncologic outcome. Methods: Patients treated for a STS with a follow-up of at least 10 years were included. Thus, 86 patients (mean age 50.5 years, range 16-86 years) treated for a STS between 1993 and 2000 were routinely controlled every 6 months. Incidence of local recurrences, distant metastases, and overall survival were analysed. Sixty-six tumour samples were available for microsatellite analysis using the former traditional method of PCR amplification at 6 loci in the neighbourhood of hMSH2, hMLH1, p53, p16, rb1, and hTR. Results: There were 30 low-grade and 56 high-grade sarcomas. The mean follow-up was 144 months (120-192 months). Twenty-nine patients died of their disease. Local recurrences were seen in 13 patients, whereas metastases were noticed in 23 patients. The overall survival was dependent on the tumour stage (p<0.05), whereas the local tumour control (incidence of local recurrence) was influenced by the surgical margin achieved (p<0.05). The molecular biologic findings revealed 67% of the investigated loci as informative. MSI was found in 6.8% of the informative loci, whereas LOH in 18.8%, respectively. LOH was present in high-grade tumours in 23.8%, whereas in 1.7% in low-grade tumours. In high-grade sarcomas, the 5-year and 10-year survival probabilities were significantly lower in LOH-positive tumours (48.6% and 38%) than in LOH-negative tumours (72.5% and 62%). Conclusion: The overall survival in soft tissue sarcoma is mainly influenced by the tumour stage. In high-grade sarcomas, the survival rate will drop even after 5 years. The detection of loss of heterozygosity represents a negative prognostic predictor in high-grade sarcomas. Microsatellite instability is a rare phenomenon supposing no relevance in the oncogenesis and tumour progression of soft tissue sarcomas.
Abstract: Purpose: Soft tissue sarcomas (STS) represent a heterotop group of tumours. Microsatellite instabilities (MSI) and loss of heterozygosity (LOH) as phenomena of a genetic instability should be analysed in STS and correlated with the long-term oncologic outcome. Methods: Patients treated for a STS with a follow-up of at least 10 years were included. ...
Show More
