Human breast cancer MDA-MB-231 cells fail to express the neurofibromin protein, lack its type I mRNA isoform and show accumulation of P-MAPK and activated Ras

Hideaki Ogata, Hirokazu Sato, Jun Takatsuka, Luigi M De Luca

Research output: Contribution to journalArticle

Abstract

Neurofibromin is a tumor suppressor protein, which is similar in function to the GTPase activating protein (GAP), p120GAP, in that it accelerates inactivation of Ras. Mutations in the NF1 gene cause neurofibromatosis type 1, NF1, an autosomal dominant disease with a diverse spectrum of clinical manifestations, including neurofibromas. Ras activation (GTP binding) is induced by the GTP exchange factor Sos and its inactivation is regulated through the GAPs (p120GAP and neurofibromin). Strikingly, neurofibromin was nearly absent in MB-231 human breast cancer cells and present in the remaining four cell lines studied, with higher levels in BT-474 and MB-453 than in MCF-7 and BT-20 cells, as tested with polyclonal antibodies to both the N-terminal as well as the C-terminal peptides. Coordinated with the near absence of neurofibromin, these cells also presented with much greater levels of P-MAPK and activated Ras. Further, RT-PCR analysis demonstrated the absence of expression of NF1 mRNA type I isoform only in the MB-231 cell lines. This result documents for the first time an altered NF1 expression at the protein and mRNA levels in MDA-MB-231 breast cancer cells.

Original languageEnglish (US)
Pages (from-to)159-164
Number of pages6
JournalCancer Letters
Volume172
Issue number2
DOIs
StatePublished - Oct 30 2001
Externally publishedYes

Fingerprint

Neurofibromin 1
RNA Isoforms
Breast Neoplasms
Guanosine Triphosphate
Proteins
Tumor Suppressor Proteins
GTPase-Activating Proteins
Cell Line
Neurofibroma
Neurofibromatosis 1
Polymerase Chain Reaction
Messenger RNA
Peptides
Mutation
Antibodies
Genes

Keywords

  • Activated ras
  • Breast cancer cells
  • Neurofibromin
  • Phosphorylated MAPK

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

Cite this

Human breast cancer MDA-MB-231 cells fail to express the neurofibromin protein, lack its type I mRNA isoform and show accumulation of P-MAPK and activated Ras. / Ogata, Hideaki; Sato, Hirokazu; Takatsuka, Jun; De Luca, Luigi M.

In: Cancer Letters, Vol. 172, No. 2, 30.10.2001, p. 159-164.

Research output: Contribution to journalArticle

@article{ff86f7fdacb1448fbdc33a6bd55fffcf,
title = "Human breast cancer MDA-MB-231 cells fail to express the neurofibromin protein, lack its type I mRNA isoform and show accumulation of P-MAPK and activated Ras",
abstract = "Neurofibromin is a tumor suppressor protein, which is similar in function to the GTPase activating protein (GAP), p120GAP, in that it accelerates inactivation of Ras. Mutations in the NF1 gene cause neurofibromatosis type 1, NF1, an autosomal dominant disease with a diverse spectrum of clinical manifestations, including neurofibromas. Ras activation (GTP binding) is induced by the GTP exchange factor Sos and its inactivation is regulated through the GAPs (p120GAP and neurofibromin). Strikingly, neurofibromin was nearly absent in MB-231 human breast cancer cells and present in the remaining four cell lines studied, with higher levels in BT-474 and MB-453 than in MCF-7 and BT-20 cells, as tested with polyclonal antibodies to both the N-terminal as well as the C-terminal peptides. Coordinated with the near absence of neurofibromin, these cells also presented with much greater levels of P-MAPK and activated Ras. Further, RT-PCR analysis demonstrated the absence of expression of NF1 mRNA type I isoform only in the MB-231 cell lines. This result documents for the first time an altered NF1 expression at the protein and mRNA levels in MDA-MB-231 breast cancer cells.",
keywords = "Activated ras, Breast cancer cells, Neurofibromin, Phosphorylated MAPK",
author = "Hideaki Ogata and Hirokazu Sato and Jun Takatsuka and {De Luca}, {Luigi M}",
year = "2001",
month = "10",
day = "30",
doi = "10.1016/S0304-3835(01)00648-6",
language = "English (US)",
volume = "172",
pages = "159--164",
journal = "Cancer Letters",
issn = "0304-3835",
publisher = "Elsevier Ireland Ltd",
number = "2",

}

TY - JOUR

T1 - Human breast cancer MDA-MB-231 cells fail to express the neurofibromin protein, lack its type I mRNA isoform and show accumulation of P-MAPK and activated Ras

AU - Ogata, Hideaki

AU - Sato, Hirokazu

AU - Takatsuka, Jun

AU - De Luca, Luigi M

PY - 2001/10/30

Y1 - 2001/10/30

N2 - Neurofibromin is a tumor suppressor protein, which is similar in function to the GTPase activating protein (GAP), p120GAP, in that it accelerates inactivation of Ras. Mutations in the NF1 gene cause neurofibromatosis type 1, NF1, an autosomal dominant disease with a diverse spectrum of clinical manifestations, including neurofibromas. Ras activation (GTP binding) is induced by the GTP exchange factor Sos and its inactivation is regulated through the GAPs (p120GAP and neurofibromin). Strikingly, neurofibromin was nearly absent in MB-231 human breast cancer cells and present in the remaining four cell lines studied, with higher levels in BT-474 and MB-453 than in MCF-7 and BT-20 cells, as tested with polyclonal antibodies to both the N-terminal as well as the C-terminal peptides. Coordinated with the near absence of neurofibromin, these cells also presented with much greater levels of P-MAPK and activated Ras. Further, RT-PCR analysis demonstrated the absence of expression of NF1 mRNA type I isoform only in the MB-231 cell lines. This result documents for the first time an altered NF1 expression at the protein and mRNA levels in MDA-MB-231 breast cancer cells.

AB - Neurofibromin is a tumor suppressor protein, which is similar in function to the GTPase activating protein (GAP), p120GAP, in that it accelerates inactivation of Ras. Mutations in the NF1 gene cause neurofibromatosis type 1, NF1, an autosomal dominant disease with a diverse spectrum of clinical manifestations, including neurofibromas. Ras activation (GTP binding) is induced by the GTP exchange factor Sos and its inactivation is regulated through the GAPs (p120GAP and neurofibromin). Strikingly, neurofibromin was nearly absent in MB-231 human breast cancer cells and present in the remaining four cell lines studied, with higher levels in BT-474 and MB-453 than in MCF-7 and BT-20 cells, as tested with polyclonal antibodies to both the N-terminal as well as the C-terminal peptides. Coordinated with the near absence of neurofibromin, these cells also presented with much greater levels of P-MAPK and activated Ras. Further, RT-PCR analysis demonstrated the absence of expression of NF1 mRNA type I isoform only in the MB-231 cell lines. This result documents for the first time an altered NF1 expression at the protein and mRNA levels in MDA-MB-231 breast cancer cells.

KW - Activated ras

KW - Breast cancer cells

KW - Neurofibromin

KW - Phosphorylated MAPK

UR - http://www.scopus.com/inward/record.url?scp=0035976039&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035976039&partnerID=8YFLogxK

U2 - 10.1016/S0304-3835(01)00648-6

DO - 10.1016/S0304-3835(01)00648-6

M3 - Article

C2 - 11566491

AN - SCOPUS:0035976039

VL - 172

SP - 159

EP - 164

JO - Cancer Letters

JF - Cancer Letters

SN - 0304-3835

IS - 2

ER -