Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

High level PHGDH expression in breast is predominantly associated with keratin 5-positive cell lineage independently of malignancy

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Harnessing data science to advance radiation oncology

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. Angiotensinogen promoter methylation predicts bevacizumab treatment response of patients with recurrent glioblastoma

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Improved prognostication of glioblastoma beyond molecular subtyping by transcriptional profiling of the tumor microenvironment

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Using microarray-based subtyping methods for breast cancer in the era of high-throughput RNA sequencing

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

We have previously reported the 2D PAGE-based proteomic profiling of a prospective cohort of 78 triple negative breast cancer (TNBC) patients, and the establishment of a cumulative TNBC protein database. Analysis of this database identified a number of proteins as being specifically overexpressed in TNBC samples. One such protein was D-3-phosphoglycerate dehydrogenase (Phgdh), a candidate oncogene. We analysed expression of Phgdh in normal and TNBC mammary tissue samples by 2D gel-based proteomics and immunohistochemistry (IHC), and show here that high-level expression of Phgdh in mammary epithelial cells is primarily associated with cell lineage, as we found that Phgdh expression was predominant in CK5-positive cells, normal as well as malignant, thus identifying an association of this protein with the basal phenotype. Quantitative IHC analysis of Phgdh expression in normal breast tissue showed high-level expression of Phgdh in normal CK5-positive mammary epithelial cells, indicating that expression of this protein was not associated with malignancy, but rather with cell lineage. However, proteomic profiling of Phgdh showed it to be expressed in two major protein forms, and that the ratio of expression between these variants was associated with malignancy. Overexpression of Phgdh in CK5-positive cell lineages, and differential protein isoform expression, was additionally found in other tissues and cancer types, suggesting that overexpression of Phgdh is generally associated with CK5 cells, and that oncogenic function may be determined by isoform expression.

OriginalsprogEngelsk
TidsskriftMolecular Oncology
Vol/bind9
Udgave nummer8
Sider (fra-til)1636-54
Antal sider19
ISSN1574-7891
DOI
StatusUdgivet - okt. 2015

ID: 45782917