Investigation of expression of wisp-1 gene in BRCA1 mutant and non-mutant breast cancer cell lines

Breast cancer is the most common malignant disease of women.The various genomic differences particularly gene expression levels are known to be associated with poor prognosis in breast cancer. The mutation of the BRCA1 gene which has a significant role in breast tumorogenesis, and associated WISP-1 gene activation inhibit the TP53 gene mediated apoptosis.In addition,suggests that TGFβ1 negatively regulating the WISP-1 gene might be a therapeutic target in breast cancer.WISP-1(CCN4) gene from the CCN protein family is a molecule which is highly expressed generally in different cancers, is associated with progression,distant metastasis, and poor prognosis in cancer.This effect shows that this gene behaves like an oncogene, however this gene was also reported as to behave as a tumor supressor in some tissue types.The change of MDA-MB-231,MDA-MB-453,MCF-7 and MDA-MB-436,WISP-1 gene expression levels in different breast cancer cell strains with various gene mutations were evaluated associated with TGFβ1 treatment in the thesis study.MDA-MB-231,MDA-MB-453, and MCF-7 cell lines have been shown to act as an oncogene in cancer formation due to the increased expression seen in the WISP-1 gene.In the MDA-MB-436 cell line,WISP-1 expression is almost nonexistent,it means that it does not have oncogenic features.In the study, it was shown that WISP-1 expression increased 6-fold in the ER-positive MCF-7 cell line with TGFβ1 administration.It has been observed that TGFβ1 increases cell proliferation in MCF-7 cell line.The decrease in the WISP-1 gene after TGFβ1 administration due to the regular operation of the TP53 pathway in MDA-MB-453,CDH1 mutant cell line indicates that TGFβ1 may be a therapeutic target.WISP-1 gene can have a biologic biomarker feature owing to the gene mutations in the breast cancer cell lines, and was shown to have a possible therapeutic target in TGFβ1,however, more detailed and clinical level studies must be conducted.