Category: Preclinical Development
Purpose: Recent remarkable efforts have been undertaken for using alternative therapeutic strategies to treat and improve the overall survival of breast cancer (BC) patients. One of these strategies is to elucidate the underlying molecular mechanisms of disease development and metastasis and discover new therapeutic targets. Our aim here was to determine the underlying molecular mechanisms of novel Transmembrane and Tetratricopeptide Repeat Containing 4 (TMTC4) in BC progression and aggressiveness.
Methods: A panel of BC cell lines were utilized to examine the expression of TMTC4 in these cells in addition to normal breast MCF10A cells. Reconstitution of TMTC4 in low-expressed cells was performed by transfection of these cells with TMTC4-based vector in addition to empty vector as a control. Functional significance of TMTC4 in BC cells was evaluated by cell proliferation, clonogenic and migration/invasion assays. In addition, immunohistochemical (IHC) studies was performed on human tissue specimens.
Results: TMTC4 was differentially expressed in BC cells versus normal breast cells. Reconstitution of TMTC4 in low-expressed BC cells increase the rate of cell growth, and migration and invasion capacities. IHC studies revealed that TMTC4 was overexpressed in BC versus normal breast tissues. There was no difference in TMTC4 expression in invasive lobular versus ductal carcinoma of BC patients. A positive correlation was established between TMTC4 and ER/PR protein expressions.
Conclusion: Taken together, TMTC4 overexpressed in BC cells and human tissues and increases the invasiveness of cancer cells. This protein can be utilized as a biomarker and potential therapeutic target for treating BC patients.
Rofaida Gaballa– Kingsville, Texas
Hamdy Ali– kingsville, Texas
Mohamed Gaballah– Kingsville, Texas
Tamer Fandy– Associate Professor, University of charleston, school of Pharmacy, Charleston, West Virginia
Hamed Ali– Kingsville, Texas
Zakaria Abd Elmageed– kingsville, Texas