Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer

B. T. F. van der Gun; C. Huisman; S. Stolzenburg; H. G. Kazemier; M. H. J. Ruiters; P. Blancafort; M. G. Rots

doi:10.1038/bjc.2013.45

Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer

B. T. F. van der Gun, C. Huisman, S. Stolzenburg, H. G. Kazemier, M. H. J. Ruiters, P. Blancafort, M. G. Rots^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

17 Citations (Scopus)

237 Downloads (Pure)

Abstract

Background: The epithelial cell adhesion molecule (EpCAM) is overexpressed on most carcinomas. Dependent on the tumour type, its overexpression is either associated with improved or worse patient survival. For ovarian cancer, however, the role of EpCAM remains unclear.

Methods: Cell survival of ovarian cancer cell lines was studied after induction or repression of endogenous EpCAM expression using siRNA/cDNA or artificial transcription factors (ATF) consisting of engineered zinc-fingers fused to either a transcriptional activator or repressor domain.

Results: Two ATFs were selected as the most potent down- and upregulator, showing at least a two-fold alteration of EpCAM protein expression compared with control. Downregulation of EpCAM expression resulted in growth inhibition in breast cancer, but showed no effect on cell growth in ovarian cancer. Induction or further upregulation of EpCAM expression decreased ovarian cancer cell survival.

Conclusion: The bidirectional ATF-based approach is uniquely suited to study cell-type-specific biological effects of EpCAM expression. Using this approach, the oncogenic function of EpCAM in breast cancer was confirmed. Despite its value as a diagnostic marker and for immunotherapy, EpCAM does not seem to represent a therapeutic target for gene expression silencing in ovarian cancer.

Original language	English
Pages (from-to)	881-886
Number of pages	6
Journal	British Jounal of Cancer
Volume	108
Issue number	4
DOIs	https://doi.org/10.1038/bjc.2013.45
Publication status	Published - 5-Mar-2013

Keywords

EpCAM
ATFs
ovarian cancer
zinc-fingers
BREAST-CANCER
EP-CAM
TRANSCRIPTION FACTORS
POOR-PROGNOSIS
OVEREXPRESSION
CELLS
CONTRIBUTES
CARCINOMA
INVASION
MARKER

Access to Document

10.1038/bjc.2013.45Licence: CC BY-NC-SA

Bidirectional modulation of endogenous EpCAM expressionFinal publisher's version, 399 KBLicence: CC BY-NC-SA

Handle.net

Persistent link

Cite this

@article{6d2470eda30b4ce9800531de49add61e,

title = "Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer",

abstract = "Background: The epithelial cell adhesion molecule (EpCAM) is overexpressed on most carcinomas. Dependent on the tumour type, its overexpression is either associated with improved or worse patient survival. For ovarian cancer, however, the role of EpCAM remains unclear.Methods: Cell survival of ovarian cancer cell lines was studied after induction or repression of endogenous EpCAM expression using siRNA/cDNA or artificial transcription factors (ATF) consisting of engineered zinc-fingers fused to either a transcriptional activator or repressor domain.Results: Two ATFs were selected as the most potent down- and upregulator, showing at least a two-fold alteration of EpCAM protein expression compared with control. Downregulation of EpCAM expression resulted in growth inhibition in breast cancer, but showed no effect on cell growth in ovarian cancer. Induction or further upregulation of EpCAM expression decreased ovarian cancer cell survival.Conclusion: The bidirectional ATF-based approach is uniquely suited to study cell-type-specific biological effects of EpCAM expression. Using this approach, the oncogenic function of EpCAM in breast cancer was confirmed. Despite its value as a diagnostic marker and for immunotherapy, EpCAM does not seem to represent a therapeutic target for gene expression silencing in ovarian cancer.",

keywords = "EpCAM, ATFs, ovarian cancer, zinc-fingers, BREAST-CANCER, EP-CAM, TRANSCRIPTION FACTORS, POOR-PROGNOSIS, OVEREXPRESSION, CELLS, CONTRIBUTES, CARCINOMA, INVASION, MARKER",

author = "{van der Gun}, {B. T. F.} and C. Huisman and S. Stolzenburg and Kazemier, {H. G.} and Ruiters, {M. H. J.} and P. Blancafort and Rots, {M. G.}",

year = "2013",

month = mar,

day = "5",

doi = "10.1038/bjc.2013.45",

language = "English",

volume = "108",

pages = "881--886",

journal = "British Jounal of Cancer",

issn = "0007-0920",

publisher = "Nature Publishing Group",

number = "4",

}

TY - JOUR

T1 - Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer

AU - van der Gun, B. T. F.

AU - Huisman, C.

AU - Stolzenburg, S.

AU - Kazemier, H. G.

AU - Ruiters, M. H. J.

AU - Blancafort, P.

AU - Rots, M. G.

PY - 2013/3/5

Y1 - 2013/3/5

N2 - Background: The epithelial cell adhesion molecule (EpCAM) is overexpressed on most carcinomas. Dependent on the tumour type, its overexpression is either associated with improved or worse patient survival. For ovarian cancer, however, the role of EpCAM remains unclear.Methods: Cell survival of ovarian cancer cell lines was studied after induction or repression of endogenous EpCAM expression using siRNA/cDNA or artificial transcription factors (ATF) consisting of engineered zinc-fingers fused to either a transcriptional activator or repressor domain.Results: Two ATFs were selected as the most potent down- and upregulator, showing at least a two-fold alteration of EpCAM protein expression compared with control. Downregulation of EpCAM expression resulted in growth inhibition in breast cancer, but showed no effect on cell growth in ovarian cancer. Induction or further upregulation of EpCAM expression decreased ovarian cancer cell survival.Conclusion: The bidirectional ATF-based approach is uniquely suited to study cell-type-specific biological effects of EpCAM expression. Using this approach, the oncogenic function of EpCAM in breast cancer was confirmed. Despite its value as a diagnostic marker and for immunotherapy, EpCAM does not seem to represent a therapeutic target for gene expression silencing in ovarian cancer.

AB - Background: The epithelial cell adhesion molecule (EpCAM) is overexpressed on most carcinomas. Dependent on the tumour type, its overexpression is either associated with improved or worse patient survival. For ovarian cancer, however, the role of EpCAM remains unclear.Methods: Cell survival of ovarian cancer cell lines was studied after induction or repression of endogenous EpCAM expression using siRNA/cDNA or artificial transcription factors (ATF) consisting of engineered zinc-fingers fused to either a transcriptional activator or repressor domain.Results: Two ATFs were selected as the most potent down- and upregulator, showing at least a two-fold alteration of EpCAM protein expression compared with control. Downregulation of EpCAM expression resulted in growth inhibition in breast cancer, but showed no effect on cell growth in ovarian cancer. Induction or further upregulation of EpCAM expression decreased ovarian cancer cell survival.Conclusion: The bidirectional ATF-based approach is uniquely suited to study cell-type-specific biological effects of EpCAM expression. Using this approach, the oncogenic function of EpCAM in breast cancer was confirmed. Despite its value as a diagnostic marker and for immunotherapy, EpCAM does not seem to represent a therapeutic target for gene expression silencing in ovarian cancer.

KW - EpCAM

KW - ATFs

KW - ovarian cancer

KW - zinc-fingers

KW - BREAST-CANCER

KW - EP-CAM

KW - TRANSCRIPTION FACTORS

KW - POOR-PROGNOSIS

KW - OVEREXPRESSION

KW - CELLS

KW - CONTRIBUTES

KW - CARCINOMA

KW - INVASION

KW - MARKER

U2 - 10.1038/bjc.2013.45

DO - 10.1038/bjc.2013.45

M3 - Article

C2 - 23403823

SN - 0007-0920

VL - 108

SP - 881

EP - 886

JO - British Jounal of Cancer

JF - British Jounal of Cancer

IS - 4

ER -

Bidirectional modulation of endogenous EpCAM expression to unravel its function in ovarian cancer

Abstract

Keywords

Access to Document

Handle.net

Fingerprint

Cite this