Gene expression profiling of initiated epidermal cells with benign or malignant tumor fates

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

High-density oligonucleotide array technology was used to search for gene expression changes that may predict or cause sporadic tumorigenesis. To reduce variation among samples, a non-transformed mouse epidermal keratinocyte clone was compared with its carcinoma-producing or papilloma-producing 7,12-dimethylbenz[a]anthracene-initiated cell derivative. The majority of the ∼12 325 genes or expressed sequence tags (ESTs) analyzed remained unaltered reflective of the clonal nature of the model. Consistent gene expression changes among biological replicates included 69 in malignancy-prone initiated cells, 46 in papilloma-precursor initiated cells and an additional 45 with changes in both initiated cell lineages. The changes covered a broad spectrum of cellular activities, implying that multiple pathways cooperate at the initiation of carcinogenesis. There was a tendency in the malignancy-prone cells for differences in proliferation and apoptosis-related genes. The benign lineage tended toward aberrant expression of genes involved in differentiation and epidermal barrier function. Several independently confirmed gene expression changes revealed plausible effectors to bypass an activated ras protein in proliferation pathways and to compromise the wild-type p53 and other apoptosis pathways at initiation of carcinogenesis. The differential expression patterns of the initiated cells are consistent with the hypothesis that changes in gene expression at initiation may cooperate with subsequent oncogenic changes to determine malignant fate. The cloned epidermal cell lineages allowed detection of putative early cancer genes in a model that is conducive to testing their direct role in epithelial multistep carcinogenesis in vitro and in vivo.

Original languageEnglish (US)
Pages (from-to)635-643
Number of pages9
JournalCarcinogenesis
Volume23
Issue number4
StatePublished - 2002

Fingerprint

Gene Expression Profiling
Gene Expression
Carcinogenesis
Papilloma
Cell Lineage
Neoplasms
Apoptosis
ras Proteins
Neoplasm Genes
Expressed Sequence Tags
Oligonucleotide Array Sequence Analysis
Keratinocytes
Genes
Clone Cells
Technology
Carcinoma

ASJC Scopus subject areas

  • Cancer Research

Cite this

@article{5c536b2fb1dc4e4a8ea90156f6329e47,
title = "Gene expression profiling of initiated epidermal cells with benign or malignant tumor fates",
abstract = "High-density oligonucleotide array technology was used to search for gene expression changes that may predict or cause sporadic tumorigenesis. To reduce variation among samples, a non-transformed mouse epidermal keratinocyte clone was compared with its carcinoma-producing or papilloma-producing 7,12-dimethylbenz[a]anthracene-initiated cell derivative. The majority of the ∼12 325 genes or expressed sequence tags (ESTs) analyzed remained unaltered reflective of the clonal nature of the model. Consistent gene expression changes among biological replicates included 69 in malignancy-prone initiated cells, 46 in papilloma-precursor initiated cells and an additional 45 with changes in both initiated cell lineages. The changes covered a broad spectrum of cellular activities, implying that multiple pathways cooperate at the initiation of carcinogenesis. There was a tendency in the malignancy-prone cells for differences in proliferation and apoptosis-related genes. The benign lineage tended toward aberrant expression of genes involved in differentiation and epidermal barrier function. Several independently confirmed gene expression changes revealed plausible effectors to bypass an activated ras protein in proliferation pathways and to compromise the wild-type p53 and other apoptosis pathways at initiation of carcinogenesis. The differential expression patterns of the initiated cells are consistent with the hypothesis that changes in gene expression at initiation may cooperate with subsequent oncogenic changes to determine malignant fate. The cloned epidermal cell lineages allowed detection of putative early cancer genes in a model that is conducive to testing their direct role in epithelial multistep carcinogenesis in vitro and in vivo.",
author = "Zhiping Wang and Yuangang Liu and Mori, {Motomi (Tomi)} and Molly Kulesz-Martin",
year = "2002",
language = "English (US)",
volume = "23",
pages = "635--643",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Gene expression profiling of initiated epidermal cells with benign or malignant tumor fates

AU - Wang, Zhiping

AU - Liu, Yuangang

AU - Mori, Motomi (Tomi)

AU - Kulesz-Martin, Molly

PY - 2002

Y1 - 2002

N2 - High-density oligonucleotide array technology was used to search for gene expression changes that may predict or cause sporadic tumorigenesis. To reduce variation among samples, a non-transformed mouse epidermal keratinocyte clone was compared with its carcinoma-producing or papilloma-producing 7,12-dimethylbenz[a]anthracene-initiated cell derivative. The majority of the ∼12 325 genes or expressed sequence tags (ESTs) analyzed remained unaltered reflective of the clonal nature of the model. Consistent gene expression changes among biological replicates included 69 in malignancy-prone initiated cells, 46 in papilloma-precursor initiated cells and an additional 45 with changes in both initiated cell lineages. The changes covered a broad spectrum of cellular activities, implying that multiple pathways cooperate at the initiation of carcinogenesis. There was a tendency in the malignancy-prone cells for differences in proliferation and apoptosis-related genes. The benign lineage tended toward aberrant expression of genes involved in differentiation and epidermal barrier function. Several independently confirmed gene expression changes revealed plausible effectors to bypass an activated ras protein in proliferation pathways and to compromise the wild-type p53 and other apoptosis pathways at initiation of carcinogenesis. The differential expression patterns of the initiated cells are consistent with the hypothesis that changes in gene expression at initiation may cooperate with subsequent oncogenic changes to determine malignant fate. The cloned epidermal cell lineages allowed detection of putative early cancer genes in a model that is conducive to testing their direct role in epithelial multistep carcinogenesis in vitro and in vivo.

AB - High-density oligonucleotide array technology was used to search for gene expression changes that may predict or cause sporadic tumorigenesis. To reduce variation among samples, a non-transformed mouse epidermal keratinocyte clone was compared with its carcinoma-producing or papilloma-producing 7,12-dimethylbenz[a]anthracene-initiated cell derivative. The majority of the ∼12 325 genes or expressed sequence tags (ESTs) analyzed remained unaltered reflective of the clonal nature of the model. Consistent gene expression changes among biological replicates included 69 in malignancy-prone initiated cells, 46 in papilloma-precursor initiated cells and an additional 45 with changes in both initiated cell lineages. The changes covered a broad spectrum of cellular activities, implying that multiple pathways cooperate at the initiation of carcinogenesis. There was a tendency in the malignancy-prone cells for differences in proliferation and apoptosis-related genes. The benign lineage tended toward aberrant expression of genes involved in differentiation and epidermal barrier function. Several independently confirmed gene expression changes revealed plausible effectors to bypass an activated ras protein in proliferation pathways and to compromise the wild-type p53 and other apoptosis pathways at initiation of carcinogenesis. The differential expression patterns of the initiated cells are consistent with the hypothesis that changes in gene expression at initiation may cooperate with subsequent oncogenic changes to determine malignant fate. The cloned epidermal cell lineages allowed detection of putative early cancer genes in a model that is conducive to testing their direct role in epithelial multistep carcinogenesis in vitro and in vivo.

UR - http://www.scopus.com/inward/record.url?scp=0036257491&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036257491&partnerID=8YFLogxK

M3 - Article

VL - 23

SP - 635

EP - 643

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 4

ER -