TITLE:
Downregulation of Telomerase Activity in Breast Cancer Impairs Cells Proliferation, Invasive Ability and Sensitizes Cells to Ultraviolet-Radiation and Adriamycin-Chemotherapy in Vitro
AUTHORS:
Xiangxia Liu, Chen Yao, Ying Lin, Sanming Wang, Hui Zhang, Shenming Wang
KEYWORDS:
Breast Cancer; Telomerase; RNA Interference; Radiation; Chemotherapy
JOURNAL NAME:
Advances in Breast Cancer Research,
Vol.2 No.3,
July
1,
2013
ABSTRACT: Backgroud: Telomerase activity, mainly regulated by
the human telomerase reverse transcriptase (hTERT) gene, plays critical roles
in tumor growth and progression through the maintenance of telomere length and
structure. Telomerase is elevated in most malignant tumors as well as in breast
cancer, the ubiquitous expression of telomerase makes it a promising
target for cancer therapy. With the goal of down regulating
telomerase activity, RNA interference technology has been applied to
specifically knockdown the hTERT gene expression in breast cancer cell line
MCF-7 and MDA-MB- 231 and determine whether h TERT-specific RNA interference technology serve
as an effective method of telomerase-based cancer therapy. Methods: Interfering p Super-retro-puro-hTERT-RNA
and the control were transfected into breast cancer cell line MCF-7 and
MDA-MB-231. The telomerase activity, cell proliferation, invasive ability and
cell response to ultraviolet-radiation or adriamycin-chemotherapy in vitro were recorded in transfected,
untransfeced and empty-transfected cells respectively. Results: Telomerase
activity was successfully suppressed in transfected cells (P 0.005). Decreased
expression of telomerase activity was associated with reduced cell proliferation
(P 0.001), migration and invasive ability (P 0.001)
and enhanced sensitivity to ultraviolet-radiation or adriamycin-chemotherapy (P 0.001). Conclusions: Telomerase activity down regulation inhibits breast cancer cell growth,
impairs cell migration, invasion and sensitizes cancer cells to radiotherapy
and chemotherapy. The hTERT-specific
RNA interference technology combined with radio-therapy and/or
chemotherapy may serve as an effective method of telomerase-based therapy in
breast cancer.