PROLIFERATIVE ROLE OF PHOSPHOGLYCERATE DEHYDROGENASE IN BREAST CANCER

Abstract

Introduction: Phosphoglycerate Dehydrogenase (PHGDH), a rate limiting enzyme in the serine synthesis pathway. Cancer cell proliferation is known to be dependent on serine metabolism for aerobic glycolysis. Hence, this study was conducted to evaluate the role of PHGDH in regulating breast cancer cell proliferation.

Methods: The relationship of PHGDH and Proliferating Cell Nuclear Antigen (PCNA), a cell proliferation marker, was first determined by performing immunohistochemical staining of the two proteins in tissue microarrays constructed from 305 breast cancer tissue samples. Next, stable knockdown of PHGDH in aggressive MDA-MB-231 breast cancer cells was carried out by shRNA-mediated silencing and the effect on cell proliferation analyzed by the AlamarBlue Assay.Chorioallantoic membrane assay was done by inoculation of knock down cell lines C3, D4 and control in chick embryos.

Results: A positive correlation was noted between PHGDH and PCNA in breast cancer tissues, whereby higher PHGDH immunostaining was associated with increased PCNA expression. Down-regulation of the PHGDH was observed to be concomitant with decreased growth of breast cancer cells in vitro and in ovo assay. Conclusion: PHGDH plays an important role in proliferation.PHGDH is therefore a potential biomarker for breast cancer cell proliferation and a molecular target for therapy.