Constitutive expression of Heregulin induces apoptosis in an erbB-2 overexpressing breast cancer cell line SKBr-3.

F. K. Guerra-Vladusic, G. Scott, V. Weaver, E. A. Vladusic, M. S. Tsai, C. C. Benz, Ruth Lupu

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

We have previously reported that Heregulin (HRG)/neu differentiation factor (NDF) induced growth arrest and cellular differentiation in breast cancer cells overexpressing erbB-2 receptor. To elucidate the cellular mechanisms underlying the growth inhibition by HRG, we developed an in vitro model by transfection of HRG cDNA into the erbB-2 overexpressing breast cancer cell line, SKBr-3. We showed that the enforced expression of HRG in SKBr-3 cells induces dramatic morphological changes and pronounced inhibition of anchorage-dependent and -independent growth. Most SKBr-3/HRG-transfected (SK/HRG) cells exhibited about 15-fold increase in size and persisted as multinucleated cells with extended flattened vacuole-filled cytoplasm with reduced cell attachment. The growth suppression of SK/HRG cells was accompanied by a reduction in S phase, the presence of a G2-M cell cycle delay, and an increase in DNA aneuploid components. In addition, DNA fragmentation assays showed that HRG induced apoptosis of SKBr-3 cells. In contrast, while HRG treatment of other erbB-2 overexpressing breast cancer cell lines led to growth arrest and cell detachment, it did not induce apoptotic features. Thus, this study demonstrates that while growth arrest and cell detachment are general effects of HRG towards erbB-2 overexpressing cells, the ability of HRG to induce apoptosis is a phenomenon confined to selective cells including SKBr-3 cells.

Original languageEnglish (US)
Pages (from-to)883-892
Number of pages10
JournalInternational Journal of Oncology
Volume15
Issue number5
StatePublished - Nov 1999
Externally publishedYes

Fingerprint

Neuregulin-1
Apoptosis
Breast Neoplasms
Cell Line
Growth
ErbB-2 Receptor
Aneuploidy
DNA Fragmentation
Vacuoles
S Phase
Transfection

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Guerra-Vladusic, F. K., Scott, G., Weaver, V., Vladusic, E. A., Tsai, M. S., Benz, C. C., & Lupu, R. (1999). Constitutive expression of Heregulin induces apoptosis in an erbB-2 overexpressing breast cancer cell line SKBr-3. International Journal of Oncology, 15(5), 883-892.

Constitutive expression of Heregulin induces apoptosis in an erbB-2 overexpressing breast cancer cell line SKBr-3. / Guerra-Vladusic, F. K.; Scott, G.; Weaver, V.; Vladusic, E. A.; Tsai, M. S.; Benz, C. C.; Lupu, Ruth.

In: International Journal of Oncology, Vol. 15, No. 5, 11.1999, p. 883-892.

Research output: Contribution to journalArticle

Guerra-Vladusic, FK, Scott, G, Weaver, V, Vladusic, EA, Tsai, MS, Benz, CC & Lupu, R 1999, 'Constitutive expression of Heregulin induces apoptosis in an erbB-2 overexpressing breast cancer cell line SKBr-3.', International Journal of Oncology, vol. 15, no. 5, pp. 883-892.
Guerra-Vladusic FK, Scott G, Weaver V, Vladusic EA, Tsai MS, Benz CC et al. Constitutive expression of Heregulin induces apoptosis in an erbB-2 overexpressing breast cancer cell line SKBr-3. International Journal of Oncology. 1999 Nov;15(5):883-892.
Guerra-Vladusic, F. K. ; Scott, G. ; Weaver, V. ; Vladusic, E. A. ; Tsai, M. S. ; Benz, C. C. ; Lupu, Ruth. / Constitutive expression of Heregulin induces apoptosis in an erbB-2 overexpressing breast cancer cell line SKBr-3. In: International Journal of Oncology. 1999 ; Vol. 15, No. 5. pp. 883-892.
@article{9077c222e70143eeb861ac524115201f,
title = "Constitutive expression of Heregulin induces apoptosis in an erbB-2 overexpressing breast cancer cell line SKBr-3.",
abstract = "We have previously reported that Heregulin (HRG)/neu differentiation factor (NDF) induced growth arrest and cellular differentiation in breast cancer cells overexpressing erbB-2 receptor. To elucidate the cellular mechanisms underlying the growth inhibition by HRG, we developed an in vitro model by transfection of HRG cDNA into the erbB-2 overexpressing breast cancer cell line, SKBr-3. We showed that the enforced expression of HRG in SKBr-3 cells induces dramatic morphological changes and pronounced inhibition of anchorage-dependent and -independent growth. Most SKBr-3/HRG-transfected (SK/HRG) cells exhibited about 15-fold increase in size and persisted as multinucleated cells with extended flattened vacuole-filled cytoplasm with reduced cell attachment. The growth suppression of SK/HRG cells was accompanied by a reduction in S phase, the presence of a G2-M cell cycle delay, and an increase in DNA aneuploid components. In addition, DNA fragmentation assays showed that HRG induced apoptosis of SKBr-3 cells. In contrast, while HRG treatment of other erbB-2 overexpressing breast cancer cell lines led to growth arrest and cell detachment, it did not induce apoptotic features. Thus, this study demonstrates that while growth arrest and cell detachment are general effects of HRG towards erbB-2 overexpressing cells, the ability of HRG to induce apoptosis is a phenomenon confined to selective cells including SKBr-3 cells.",
author = "Guerra-Vladusic, {F. K.} and G. Scott and V. Weaver and Vladusic, {E. A.} and Tsai, {M. S.} and Benz, {C. C.} and Ruth Lupu",
year = "1999",
month = "11",
language = "English (US)",
volume = "15",
pages = "883--892",
journal = "International Journal of Oncology",
issn = "1019-6439",
publisher = "Spandidos Publications",
number = "5",

}

TY - JOUR

T1 - Constitutive expression of Heregulin induces apoptosis in an erbB-2 overexpressing breast cancer cell line SKBr-3.

AU - Guerra-Vladusic, F. K.

AU - Scott, G.

AU - Weaver, V.

AU - Vladusic, E. A.

AU - Tsai, M. S.

AU - Benz, C. C.

AU - Lupu, Ruth

PY - 1999/11

Y1 - 1999/11

N2 - We have previously reported that Heregulin (HRG)/neu differentiation factor (NDF) induced growth arrest and cellular differentiation in breast cancer cells overexpressing erbB-2 receptor. To elucidate the cellular mechanisms underlying the growth inhibition by HRG, we developed an in vitro model by transfection of HRG cDNA into the erbB-2 overexpressing breast cancer cell line, SKBr-3. We showed that the enforced expression of HRG in SKBr-3 cells induces dramatic morphological changes and pronounced inhibition of anchorage-dependent and -independent growth. Most SKBr-3/HRG-transfected (SK/HRG) cells exhibited about 15-fold increase in size and persisted as multinucleated cells with extended flattened vacuole-filled cytoplasm with reduced cell attachment. The growth suppression of SK/HRG cells was accompanied by a reduction in S phase, the presence of a G2-M cell cycle delay, and an increase in DNA aneuploid components. In addition, DNA fragmentation assays showed that HRG induced apoptosis of SKBr-3 cells. In contrast, while HRG treatment of other erbB-2 overexpressing breast cancer cell lines led to growth arrest and cell detachment, it did not induce apoptotic features. Thus, this study demonstrates that while growth arrest and cell detachment are general effects of HRG towards erbB-2 overexpressing cells, the ability of HRG to induce apoptosis is a phenomenon confined to selective cells including SKBr-3 cells.

AB - We have previously reported that Heregulin (HRG)/neu differentiation factor (NDF) induced growth arrest and cellular differentiation in breast cancer cells overexpressing erbB-2 receptor. To elucidate the cellular mechanisms underlying the growth inhibition by HRG, we developed an in vitro model by transfection of HRG cDNA into the erbB-2 overexpressing breast cancer cell line, SKBr-3. We showed that the enforced expression of HRG in SKBr-3 cells induces dramatic morphological changes and pronounced inhibition of anchorage-dependent and -independent growth. Most SKBr-3/HRG-transfected (SK/HRG) cells exhibited about 15-fold increase in size and persisted as multinucleated cells with extended flattened vacuole-filled cytoplasm with reduced cell attachment. The growth suppression of SK/HRG cells was accompanied by a reduction in S phase, the presence of a G2-M cell cycle delay, and an increase in DNA aneuploid components. In addition, DNA fragmentation assays showed that HRG induced apoptosis of SKBr-3 cells. In contrast, while HRG treatment of other erbB-2 overexpressing breast cancer cell lines led to growth arrest and cell detachment, it did not induce apoptotic features. Thus, this study demonstrates that while growth arrest and cell detachment are general effects of HRG towards erbB-2 overexpressing cells, the ability of HRG to induce apoptosis is a phenomenon confined to selective cells including SKBr-3 cells.

UR - http://www.scopus.com/inward/record.url?scp=0033227253&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033227253&partnerID=8YFLogxK

M3 - Article

VL - 15

SP - 883

EP - 892

JO - International Journal of Oncology

JF - International Journal of Oncology

SN - 1019-6439

IS - 5

ER -