Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells

Srinivas Venkateswarlu, Dawn M. Dawson, Patricia St Clair, Anjana Gupta, James K.V. Willson, Michael G Brattain

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

The aim of this study was to determine whether constitutive ErbB2 activation controls growth and apoptosis in colon cancer cells. Growth arrested GEO cells showed constitutive activation of ErbB2 in the absence of exogenous growth factors or serum supplementation. Higher levels of heregulin and ErbB2 activation were observed in the growth-arrested state and cell cycle re-entry was independent of exogenous growth factors. Blockade of ErbB2 activation by heregulin neutralizing antibodies and by AG879 resulted in prevention of cell cycle re-entry. This indicated that autocrine heregulin activity was responsible for growth factor independence and for cell cycle re-entry. Activation of ErbB2 was the result of heregulin mediated interaction with ErbB3 and generated downstream activation of the ERK and the PI3K/AKT pathways. Heregulin neutralizing antibody treatment of growth arrested GEO cells also generated apoptosis as reflected by PARP cleavage and DNA fragmentation indicating a cell survival signal was also induced by the constitutively activated ErbB2. The activation of AKT but not the MAPK pathway was responsible for cell survival in these cells.

Original languageEnglish (US)
Pages (from-to)78-86
Number of pages9
JournalOncogene
Volume21
Issue number1
DOIs
StatePublished - Jan 3 2002

Fingerprint

Neuregulin-1
Colonic Neoplasms
Intercellular Signaling Peptides and Proteins
Apoptosis
Cell Cycle
Growth
Neutralizing Antibodies
Cell Survival
DNA Fragmentation
Phosphatidylinositol 3-Kinases
Serum

Keywords

  • Constitutive activation
  • Erbb2
  • Heregulin

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Venkateswarlu, S., Dawson, D. M., St Clair, P., Gupta, A., Willson, J. K. V., & Brattain, M. G. (2002). Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells. Oncogene, 21(1), 78-86. https://doi.org/10.1038/sj.onc.1205011

Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells. / Venkateswarlu, Srinivas; Dawson, Dawn M.; St Clair, Patricia; Gupta, Anjana; Willson, James K.V.; Brattain, Michael G.

In: Oncogene, Vol. 21, No. 1, 03.01.2002, p. 78-86.

Research output: Contribution to journalArticle

Venkateswarlu, S, Dawson, DM, St Clair, P, Gupta, A, Willson, JKV & Brattain, MG 2002, 'Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells', Oncogene, vol. 21, no. 1, pp. 78-86. https://doi.org/10.1038/sj.onc.1205011
Venkateswarlu S, Dawson DM, St Clair P, Gupta A, Willson JKV, Brattain MG. Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells. Oncogene. 2002 Jan 3;21(1):78-86. https://doi.org/10.1038/sj.onc.1205011
Venkateswarlu, Srinivas ; Dawson, Dawn M. ; St Clair, Patricia ; Gupta, Anjana ; Willson, James K.V. ; Brattain, Michael G. / Autocrine heregulin generates growth factor independence and blocks apoptosis in colon cancer cells. In: Oncogene. 2002 ; Vol. 21, No. 1. pp. 78-86.
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