Constitutive activation of MAPK/ERK inhibits prostate cancer cell proliferation through upregulation of BRCA2

Corrigendum in: /10.3892/ijo.2016.3487

  • Authors:
    • Loredana Moro
    • Arnaldo A. Arbini
    • Ersilia Marra
    • Margherita Greco
  • View Affiliations

  • Published online on: January 1, 2007     https://doi.org/10.3892/ijo.30.1.217
  • Pages: 217-224
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Abstract

BRCA2 is central to an utterly diverse biological behavior elicited after integrin-mediated normal and prostate cancer cell adhesion to basement membrane (BM) and extracellular matrix (ECM) proteins. Unlike normal cells, adhesive stimuli in cancer cells activate PI 3-kinase/AKT signaling resulting in BRCA2 degradation and unchecked cancer cell proliferation and metastasis. However, the precise mechanisms involved in normal BRCA2 homeostasis are unknown. We investigated ERK and AKT phosphorylation in normal (PNT1A) and cancer (PC-3) prostate cells after adhesion to ECM and the effects upon BRCA2 and cell proliferation. PNT1A cell adhesion to ECM triggered MAPK/ERK signaling resulting in upregulation of BRCA2 mRNA and protein, with negligible effects upon cell proliferation. Disruption of MAPK/ERK with PD98059 prevented any BRCA2 upregulation inhibiting DNA synthesis below basal levels. PC-3 cells exhibited a defective MAPK/ERK pathway that was unresponsive to adhesion to the ECM, which instead triggered PI 3-kinase/AKT signaling leading to BRCA2 protein depletion and cell proliferation. Reconstitution of MAPK/ERK by recombinant expression of a constitutively active form of MAPK kinase 1 (MEK1) effectively reversed the neoplastic phenotype by increasing BRCA2 expression and preventing any aberrant cell proliferation at rest and upon interaction with ECM proteins. Our results suggest that aberrant loss of MAPK/ERK activity in prostate cancer may play a pivotal role in the malignant phenotype, and provide evidence that interventions aimed at bypassing the signaling block are able to effectively reverse neoplastic unchecked cell proliferation.

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January 2007
Volume 30 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Moro L, Arbini AA, Marra E and Greco M: Constitutive activation of MAPK/ERK inhibits prostate cancer cell proliferation through upregulation of BRCA2 Corrigendum in /10.3892/ijo.2016.3487. Int J Oncol 30: 217-224, 2007
APA
Moro, L., Arbini, A.A., Marra, E., & Greco, M. (2007). Constitutive activation of MAPK/ERK inhibits prostate cancer cell proliferation through upregulation of BRCA2 Corrigendum in /10.3892/ijo.2016.3487. International Journal of Oncology, 30, 217-224. https://doi.org/10.3892/ijo.30.1.217
MLA
Moro, L., Arbini, A. A., Marra, E., Greco, M."Constitutive activation of MAPK/ERK inhibits prostate cancer cell proliferation through upregulation of BRCA2 Corrigendum in /10.3892/ijo.2016.3487". International Journal of Oncology 30.1 (2007): 217-224.
Chicago
Moro, L., Arbini, A. A., Marra, E., Greco, M."Constitutive activation of MAPK/ERK inhibits prostate cancer cell proliferation through upregulation of BRCA2 Corrigendum in /10.3892/ijo.2016.3487". International Journal of Oncology 30, no. 1 (2007): 217-224. https://doi.org/10.3892/ijo.30.1.217