The differential effect of USP7 on breast cancer cell lines

THE DIFFERENTIAL EFFECT OF USP7 ON BREAST CANCER CELL LINES Breast cancer has the highest mortality rate among women compared to other various types of cancer. As a multi-stage and complicated cancer type, breast cancer might be initiated by various stimuli. Most of the breast cancer patients have been diagnosed with a familial predisposition due to the poor genetical heritage. Investigation of mutated proteins and affected pathways are bare essential to develop an effective cure for targeted therapy. In the current study, potential anti-cancer activity of USP7 gene supression has been evaluated by in vitro cell proliferation analysis, the examination of alterations in gene and protein expression profile, three dimensional sphere formation capacity and colony forming unit assays. The small molecule inhibitor of USP7 enzyme in addition to small interfering RNA (siRNA) and lentiviral short hairpin vector (shRNA) has been used as targeting strategies against USP7. MCF7 and T47D human breast cancer cell lines, which maintain different P53 gene status, have been used to determine whether the anti-cancer effect of USP7 enzyme is p53 dependent or in-dependent. Overall, a significant anticancer activity of USP7 inhibition has been detected in vitro for the breast cancer cell lines. Many molecular, physiological and morphological changes have been observed upon USP7 inactivation in all of the three different experimental strategy indicating the potential anti-cancer activity of USP7 blockage. USP7 inactivation inhibited the cancer cell proliferation, invasion and metastasis in MCF7 and T47D cell lines. However, further investigation should also be conducted with the purpose of comprehending the exact molecular mechanism which underlies in the total effect of USP7 on tumorigenic progression. This is the first study in literature which offers a critical examination of the differential effects of targeting USP7 enzyme by both at protein and gene levels in MCF7 and T47D cell lines.