The role of interferon-gamma and vitamin-A in modulating telomerase activity in breast cancer patients.
Telomerase is a ribonucloprotein enzyme that appears to play a role in carcinogenesis. To understand the regulatory mechanisms which govern telomerase activity, we used telomeric repeat amplification protocol (TRAP) to quantitate and compare telomerase activity in cultured peripheral blood mononuclear cells (PBMCs) with and without INF-gamma in breast cancer patients. Serum levels of IFN-gamma and vitamin-A were also measured to look for a possible influence of these chemotherapeutic agents on telomerase activity. 23 premenopausal breast carcinoma patients (8 with clinical stage 11, 8 stage III and 7 stage IV) and ten age and menstrual stage matched healthy controls were studied. Before surgery, telomerase activity and IFN-gamma levels were significantly higher (P<0.001, P<0.05 respectively) in patients than controls and were associated with significant lower (P<0.001) serum level of vitamin-A. After surgery, chemotherapy for 3 cycles and oral vitamin-A, a sharp reduction in telomerase activity and serum IFN-gamma levels was observed in all groups of patients compared to the controls. Cultivation of PBMCs in the presence of IFN-gamma caused up-regulation (about 25%) of telomerase activity. However, a significant positive correlation (r = 0.941; P < 0.001) in telomerase activity was observed between cultured PBMCs with and without IFN-gamma in all breast cancer patients before treatment. Positive correlation was also found between serum levels of IFN-gamma and telomerase activity of cultured PBMCs with and without IFN-gamma (P< 0.01). In contrast, negative correlations were observed between serum levels of vitamin-A and telomerase activity and serum levels of IFN-gamma (P < 0.01). It is concluded that IFN-gamma and vitamin-A may modulate telomerase activity in breast cancer patients and this should be considered in developing new strategies to control cancer cell growth.
Hussein
Amina El-Sayed
Ael-S
Department of Immunology, Medical Research Institute, Alexandria University, Alexandria, Egypt.
El-Moneim
Nadia A Abd
NA
Mahmoud
Mervat M
MM
Abdel -Baky
Mostafa M
MM
D000328:Adult; D001943:Breast Neoplasms / Q000097:blood / Q000201:enzymology* / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000276:immunology; D008875:Middle Aged; D019098:Telomerase / Q000097:blood*; D014801:Vitamin A / Q000097:blood*
D014801:Vitamin A; D007371:Interferon-gamma; D019098:Telomerase