Low-concentration vemurafenib induces the proliferation and invasion of human HaCaT keratinocytes through mitogen-activated protein kinase pathway activation

MiRyung Roh, Jung Min Kim, Sang Hee Lee, Hong Sun Jang, Kyu Hyun Park, Kee Yang Chung, SunYoung Rha

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Cutaneous squamous cell carcinomas and keratoacanthomas commonly occur in patients treated with BRAF inhibitors. We investigated the effect of the BRAF inhibitor vemurafenib on normal immortalized human HaCaT keratinocytes to explore the mechanism of hyperproliferative cutaneous neoplasia associated with the use of BRAF inhibitors. Vemurafenib induced an increase in viable cell number in BRAF wild-type cell lines (SK-MEL-2 and HaCaT) but not in BRAF mutant cell lines (SK-MEL-24 and G361). In HaCaT keratinocytes, a low concentration (2 μmol/L) of vemurafenib increased cell proliferation and activated mitogen-activated protein kinase kinase/extracellular signal-regulated kinase in a CRAF-dependent manner. Invasiveness of HaCaT cells in a Matrigel assay significantly increased upon cultivation of cells with 2 μmol/L vemurafenib for 24 h. Gelatin zymography, reverse transcription polymerase chain reaction and western blot results revealed that 2 μmol/L vemurafenib treatment increased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities in HaCaT cells. These results offer additional insight into the complex mechanism of paradoxical mitogen-activated protein kinase signaling involved in hyperproliferative cutaneous neoplasias that arise after BRAF inhibition and suggest a possible role for MMP in tumor progression and invasion.

Original languageEnglish
Pages (from-to)881-888
Number of pages8
JournalJournal of Dermatology
Volume42
Issue number9
DOIs
Publication statusPublished - 2015 Sep 1

Fingerprint

Mitogen-Activated Protein Kinases
Keratinocytes
Skin
Keratoacanthoma
Cell Line
Neoplasms
Matrix Metalloproteinase 2
Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
Matrix Metalloproteinase 9
Gelatin
Matrix Metalloproteinases
Reverse Transcription
Squamous Cell Carcinoma
Cell Count
Western Blotting
Cell Proliferation
PLX4032
Polymerase Chain Reaction
Therapeutics

All Science Journal Classification (ASJC) codes

  • Dermatology

Cite this

@article{80704763e347421d96c78375a1d565e5,
title = "Low-concentration vemurafenib induces the proliferation and invasion of human HaCaT keratinocytes through mitogen-activated protein kinase pathway activation",
abstract = "Cutaneous squamous cell carcinomas and keratoacanthomas commonly occur in patients treated with BRAF inhibitors. We investigated the effect of the BRAF inhibitor vemurafenib on normal immortalized human HaCaT keratinocytes to explore the mechanism of hyperproliferative cutaneous neoplasia associated with the use of BRAF inhibitors. Vemurafenib induced an increase in viable cell number in BRAF wild-type cell lines (SK-MEL-2 and HaCaT) but not in BRAF mutant cell lines (SK-MEL-24 and G361). In HaCaT keratinocytes, a low concentration (2 μmol/L) of vemurafenib increased cell proliferation and activated mitogen-activated protein kinase kinase/extracellular signal-regulated kinase in a CRAF-dependent manner. Invasiveness of HaCaT cells in a Matrigel assay significantly increased upon cultivation of cells with 2 μmol/L vemurafenib for 24 h. Gelatin zymography, reverse transcription polymerase chain reaction and western blot results revealed that 2 μmol/L vemurafenib treatment increased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities in HaCaT cells. These results offer additional insight into the complex mechanism of paradoxical mitogen-activated protein kinase signaling involved in hyperproliferative cutaneous neoplasias that arise after BRAF inhibition and suggest a possible role for MMP in tumor progression and invasion.",
author = "MiRyung Roh and Kim, {Jung Min} and Lee, {Sang Hee} and Jang, {Hong Sun} and Park, {Kyu Hyun} and Chung, {Kee Yang} and SunYoung Rha",
year = "2015",
month = "9",
day = "1",
doi = "10.1111/1346-8138.12950",
language = "English",
volume = "42",
pages = "881--888",
journal = "Journal of Dermatology",
issn = "0385-2407",
publisher = "Wiley-Blackwell",
number = "9",

}

Low-concentration vemurafenib induces the proliferation and invasion of human HaCaT keratinocytes through mitogen-activated protein kinase pathway activation. / Roh, MiRyung; Kim, Jung Min; Lee, Sang Hee; Jang, Hong Sun; Park, Kyu Hyun; Chung, Kee Yang; Rha, SunYoung.

In: Journal of Dermatology, Vol. 42, No. 9, 01.09.2015, p. 881-888.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Low-concentration vemurafenib induces the proliferation and invasion of human HaCaT keratinocytes through mitogen-activated protein kinase pathway activation

AU - Roh, MiRyung

AU - Kim, Jung Min

AU - Lee, Sang Hee

AU - Jang, Hong Sun

AU - Park, Kyu Hyun

AU - Chung, Kee Yang

AU - Rha, SunYoung

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Cutaneous squamous cell carcinomas and keratoacanthomas commonly occur in patients treated with BRAF inhibitors. We investigated the effect of the BRAF inhibitor vemurafenib on normal immortalized human HaCaT keratinocytes to explore the mechanism of hyperproliferative cutaneous neoplasia associated with the use of BRAF inhibitors. Vemurafenib induced an increase in viable cell number in BRAF wild-type cell lines (SK-MEL-2 and HaCaT) but not in BRAF mutant cell lines (SK-MEL-24 and G361). In HaCaT keratinocytes, a low concentration (2 μmol/L) of vemurafenib increased cell proliferation and activated mitogen-activated protein kinase kinase/extracellular signal-regulated kinase in a CRAF-dependent manner. Invasiveness of HaCaT cells in a Matrigel assay significantly increased upon cultivation of cells with 2 μmol/L vemurafenib for 24 h. Gelatin zymography, reverse transcription polymerase chain reaction and western blot results revealed that 2 μmol/L vemurafenib treatment increased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities in HaCaT cells. These results offer additional insight into the complex mechanism of paradoxical mitogen-activated protein kinase signaling involved in hyperproliferative cutaneous neoplasias that arise after BRAF inhibition and suggest a possible role for MMP in tumor progression and invasion.

AB - Cutaneous squamous cell carcinomas and keratoacanthomas commonly occur in patients treated with BRAF inhibitors. We investigated the effect of the BRAF inhibitor vemurafenib on normal immortalized human HaCaT keratinocytes to explore the mechanism of hyperproliferative cutaneous neoplasia associated with the use of BRAF inhibitors. Vemurafenib induced an increase in viable cell number in BRAF wild-type cell lines (SK-MEL-2 and HaCaT) but not in BRAF mutant cell lines (SK-MEL-24 and G361). In HaCaT keratinocytes, a low concentration (2 μmol/L) of vemurafenib increased cell proliferation and activated mitogen-activated protein kinase kinase/extracellular signal-regulated kinase in a CRAF-dependent manner. Invasiveness of HaCaT cells in a Matrigel assay significantly increased upon cultivation of cells with 2 μmol/L vemurafenib for 24 h. Gelatin zymography, reverse transcription polymerase chain reaction and western blot results revealed that 2 μmol/L vemurafenib treatment increased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities in HaCaT cells. These results offer additional insight into the complex mechanism of paradoxical mitogen-activated protein kinase signaling involved in hyperproliferative cutaneous neoplasias that arise after BRAF inhibition and suggest a possible role for MMP in tumor progression and invasion.

UR - http://www.scopus.com/inward/record.url?scp=84940953698&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940953698&partnerID=8YFLogxK

U2 - 10.1111/1346-8138.12950

DO - 10.1111/1346-8138.12950

M3 - Article

C2 - 26047064

AN - SCOPUS:84940953698

VL - 42

SP - 881

EP - 888

JO - Journal of Dermatology

JF - Journal of Dermatology

SN - 0385-2407

IS - 9

ER -