Profile of gene expression induced by the tumour promotor TPA in murine epithelial cells
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Profile of gene expression induced by the tumour promotor TPA in murine epithelial cells. / Schlingemann, Joerg; Hess, Jochen; Wrobel, Gunnar; Breitenbach, Ute; Gebhardt, Christoffer; Steinlein, Peter; Kramer, Heidi; Fürstenberger, Gerhard; Hahn, Meinhard; Angel, Peter; Lichter, Peter.
In: INT J CANCER, Vol. 104, No. 6, 10.05.2003, p. 699-708.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Profile of gene expression induced by the tumour promotor TPA in murine epithelial cells
AU - Schlingemann, Joerg
AU - Hess, Jochen
AU - Wrobel, Gunnar
AU - Breitenbach, Ute
AU - Gebhardt, Christoffer
AU - Steinlein, Peter
AU - Kramer, Heidi
AU - Fürstenberger, Gerhard
AU - Hahn, Meinhard
AU - Angel, Peter
AU - Lichter, Peter
N1 - Copyright 2003 Wiley-Liss, Inc.
PY - 2003/5/10
Y1 - 2003/5/10
N2 - Malignant transformation of mouse skin by chemical carcinogens and tumour promoters, such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), is a multistage process that leads to squamous cell carcinoma (SCC) formation. In an effort to identify tumour-associated genes, we studied the influence of short-term TPA-treatment on the gene expression profile of murine skin. A comprehensive microarray with some 5,000 murine gene specific cDNA fragments was established and hybridised with pooled RNA derived from control and TPA-treated dorsal skin samples. Of these genes, 54 were up- and 35 were down-regulated upon TPA application. Additionally, we performed suppression subtractive hybridisation (SSH) with respective RNA pools to generate and analyse a cDNA library enriched for TPA-inducible genes. Expression data of selected genes were confirmed by quantitative real-time PCR and Northern blot analysis. Comparison of microarray and SSH data revealed that 26% of up-regulated genes identified by expression profiling matched with those present in the SSH library. Besides numerous known genes, we identified a large set of unknown cDNAs that represent previously unrecognised TPA-regulated genes in murine skin with potential function in tumour promotion. Additionally, some TPA-induced genes, such as Sprr1A, Saa3, JunB, Il4ralpha, Gp38, RalGDS and Slpi exhibit high basal level in advanced stages of skin carcinogenesis, suggesting that at least a subgroup of the identified TPA-regulated genes may contribute to tumour progression and metastasis.
AB - Malignant transformation of mouse skin by chemical carcinogens and tumour promoters, such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), is a multistage process that leads to squamous cell carcinoma (SCC) formation. In an effort to identify tumour-associated genes, we studied the influence of short-term TPA-treatment on the gene expression profile of murine skin. A comprehensive microarray with some 5,000 murine gene specific cDNA fragments was established and hybridised with pooled RNA derived from control and TPA-treated dorsal skin samples. Of these genes, 54 were up- and 35 were down-regulated upon TPA application. Additionally, we performed suppression subtractive hybridisation (SSH) with respective RNA pools to generate and analyse a cDNA library enriched for TPA-inducible genes. Expression data of selected genes were confirmed by quantitative real-time PCR and Northern blot analysis. Comparison of microarray and SSH data revealed that 26% of up-regulated genes identified by expression profiling matched with those present in the SSH library. Besides numerous known genes, we identified a large set of unknown cDNAs that represent previously unrecognised TPA-regulated genes in murine skin with potential function in tumour promotion. Additionally, some TPA-induced genes, such as Sprr1A, Saa3, JunB, Il4ralpha, Gp38, RalGDS and Slpi exhibit high basal level in advanced stages of skin carcinogenesis, suggesting that at least a subgroup of the identified TPA-regulated genes may contribute to tumour progression and metastasis.
KW - Animals
KW - Biomarkers, Tumor
KW - Blotting, Northern
KW - Carcinogens
KW - DNA Primers
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation, Neoplastic
KW - Gene Library
KW - In Situ Hybridization
KW - Keratinocytes
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Neoplasm Proteins
KW - Nucleic Acid Hybridization
KW - Polymerase Chain Reaction
KW - RNA, Neoplasm
KW - Skin
KW - Skin Neoplasms
KW - Subtraction Technique
KW - Tetradecanoylphorbol Acetate
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1002/ijc.11008
DO - 10.1002/ijc.11008
M3 - SCORING: Journal article
C2 - 12640676
VL - 104
SP - 699
EP - 708
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
IS - 6
ER -