Modulation of human epidermal cell response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by epidermal growth factor

Miguel A. Rea, Marjorie A. Phillips, Lea Ann Degraffenried, Qin Qin, Robert H. Rice

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Cultured human epidermal cells were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the presence or absence of epidermal growth factor (EGF). In both normal keratinocytes and a spontaneously immortalized keratinocyte (SIK) line, TCDD treatment in the absence of EGF induced a marked reduction in colony size and cell number, and it perturbed colony morphology. These effects were largely prevented by EGF, indicating that growth factor action in the cellular microenvironment may considerably modify TCDD action in target cells. Both TCDD and EGF substantially reduced expression of the differentiation markers keratin 1 and keratin 10 in the normal and immortalized cells, and did so in an additive fashion. The cells did not display a general loss of differentiated function, since several other markers, including involucrin, were little affected. EGF dramatically stimulated telomerase activity in SIK cultures, and TCDD prevented this action but not by reducing cell growth. However, EGF did not stimulate telomerase activity in normal human epidermal cells despite an evident increase in their growth. The growth factor stimulation of telomerase in the minimally deviated SIK line suggests that derepression of enzyme activity in normal cells may occur in a stepwise fashion during neoplastic progression. TCDD could act as a late stage tumor promoter by selecting for variants in which telomerase is constitutively active.

Original languageEnglish (US)
Pages (from-to)479-483
Number of pages5
JournalCarcinogenesis
Volume19
Issue number3
DOIs
StatePublished - Mar 1998

Fingerprint

Epidermal Growth Factor
Telomerase
Keratinocytes
Intercellular Signaling Peptides and Proteins
Keratin-1
Keratin-10
Cellular Microenvironment
Differentiation Antigens
Growth
Polychlorinated Dibenzodioxins
Carcinogens
Cell Count
Enzymes

ASJC Scopus subject areas

  • Cancer Research

Cite this

Modulation of human epidermal cell response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by epidermal growth factor. / Rea, Miguel A.; Phillips, Marjorie A.; Degraffenried, Lea Ann; Qin, Qin; Rice, Robert H.

In: Carcinogenesis, Vol. 19, No. 3, 03.1998, p. 479-483.

Research output: Contribution to journalArticle

Rea, Miguel A. ; Phillips, Marjorie A. ; Degraffenried, Lea Ann ; Qin, Qin ; Rice, Robert H. / Modulation of human epidermal cell response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by epidermal growth factor. In: Carcinogenesis. 1998 ; Vol. 19, No. 3. pp. 479-483.
@article{557a194ad7184ecd890de993953aea28,
title = "Modulation of human epidermal cell response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by epidermal growth factor",
abstract = "Cultured human epidermal cells were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the presence or absence of epidermal growth factor (EGF). In both normal keratinocytes and a spontaneously immortalized keratinocyte (SIK) line, TCDD treatment in the absence of EGF induced a marked reduction in colony size and cell number, and it perturbed colony morphology. These effects were largely prevented by EGF, indicating that growth factor action in the cellular microenvironment may considerably modify TCDD action in target cells. Both TCDD and EGF substantially reduced expression of the differentiation markers keratin 1 and keratin 10 in the normal and immortalized cells, and did so in an additive fashion. The cells did not display a general loss of differentiated function, since several other markers, including involucrin, were little affected. EGF dramatically stimulated telomerase activity in SIK cultures, and TCDD prevented this action but not by reducing cell growth. However, EGF did not stimulate telomerase activity in normal human epidermal cells despite an evident increase in their growth. The growth factor stimulation of telomerase in the minimally deviated SIK line suggests that derepression of enzyme activity in normal cells may occur in a stepwise fashion during neoplastic progression. TCDD could act as a late stage tumor promoter by selecting for variants in which telomerase is constitutively active.",
author = "Rea, {Miguel A.} and Phillips, {Marjorie A.} and Degraffenried, {Lea Ann} and Qin Qin and Rice, {Robert H.}",
year = "1998",
month = "3",
doi = "10.1093/carcin/19.3.479",
language = "English (US)",
volume = "19",
pages = "479--483",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Modulation of human epidermal cell response to 2,3,7,8-tetrachlorodibenzo-p-dioxin by epidermal growth factor

AU - Rea, Miguel A.

AU - Phillips, Marjorie A.

AU - Degraffenried, Lea Ann

AU - Qin, Qin

AU - Rice, Robert H.

PY - 1998/3

Y1 - 1998/3

N2 - Cultured human epidermal cells were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the presence or absence of epidermal growth factor (EGF). In both normal keratinocytes and a spontaneously immortalized keratinocyte (SIK) line, TCDD treatment in the absence of EGF induced a marked reduction in colony size and cell number, and it perturbed colony morphology. These effects were largely prevented by EGF, indicating that growth factor action in the cellular microenvironment may considerably modify TCDD action in target cells. Both TCDD and EGF substantially reduced expression of the differentiation markers keratin 1 and keratin 10 in the normal and immortalized cells, and did so in an additive fashion. The cells did not display a general loss of differentiated function, since several other markers, including involucrin, were little affected. EGF dramatically stimulated telomerase activity in SIK cultures, and TCDD prevented this action but not by reducing cell growth. However, EGF did not stimulate telomerase activity in normal human epidermal cells despite an evident increase in their growth. The growth factor stimulation of telomerase in the minimally deviated SIK line suggests that derepression of enzyme activity in normal cells may occur in a stepwise fashion during neoplastic progression. TCDD could act as a late stage tumor promoter by selecting for variants in which telomerase is constitutively active.

AB - Cultured human epidermal cells were treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the presence or absence of epidermal growth factor (EGF). In both normal keratinocytes and a spontaneously immortalized keratinocyte (SIK) line, TCDD treatment in the absence of EGF induced a marked reduction in colony size and cell number, and it perturbed colony morphology. These effects were largely prevented by EGF, indicating that growth factor action in the cellular microenvironment may considerably modify TCDD action in target cells. Both TCDD and EGF substantially reduced expression of the differentiation markers keratin 1 and keratin 10 in the normal and immortalized cells, and did so in an additive fashion. The cells did not display a general loss of differentiated function, since several other markers, including involucrin, were little affected. EGF dramatically stimulated telomerase activity in SIK cultures, and TCDD prevented this action but not by reducing cell growth. However, EGF did not stimulate telomerase activity in normal human epidermal cells despite an evident increase in their growth. The growth factor stimulation of telomerase in the minimally deviated SIK line suggests that derepression of enzyme activity in normal cells may occur in a stepwise fashion during neoplastic progression. TCDD could act as a late stage tumor promoter by selecting for variants in which telomerase is constitutively active.

UR - http://www.scopus.com/inward/record.url?scp=0031879021&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031879021&partnerID=8YFLogxK

U2 - 10.1093/carcin/19.3.479

DO - 10.1093/carcin/19.3.479

M3 - Article

VL - 19

SP - 479

EP - 483

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 3

ER -