Publication Date:
2004-02-07
Description:
Stromal cells can have a significant impact on the carcinogenic process in adjacent epithelia. The role of transforming growth factor-beta (TGF-beta) signaling in such epithelial-mesenchymal interactions was determined by conditional inactivation of the TGF-beta type II receptor gene in mouse fibroblasts (Tgfbr2fspKO). The loss of TGF-beta responsiveness in fibroblasts resulted in intraepithelial neoplasia in prostate and invasive squamous cell carcinoma of the forestomach, both associated with an increased abundance of stromal cells. Activation of paracrine hepatocyte growth factor (HGF) signaling was identified as one possible mechanism for stimulation of epithelial proliferation. Thus, TGF-beta signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bhowmick, Neil A -- Chytil, Anna -- Plieth, David -- Gorska, Agnieszka E -- Dumont, Nancy -- Shappell, Scott -- Washington, M Kay -- Neilson, Eric G -- Moses, Harold L -- AR41943/AR/NIAMS NIH HHS/ -- CA102162/CA/NCI NIH HHS/ -- CA68485/CA/NCI NIH HHS/ -- CA85492/CA/NCI NIH HHS/ -- DK46282/DK/NIDDK NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 6;303(5659):848-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14764882" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Carcinoma, Squamous Cell/etiology/metabolism/pathology
;
Cell Division
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*Cell Transformation, Neoplastic
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Cells, Cultured
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Epithelial Cells/*physiology
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Female
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Fibroblasts/*physiology
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Hepatocyte Growth Factor/metabolism
;
Male
;
Mice
;
Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Neoplasms, Glandular and Epithelial/*etiology/metabolism/pathology
;
Prostate/cytology/metabolism/pathology
;
Prostatic Intraepithelial Neoplasia/etiology/metabolism/pathology
;
Protein-Serine-Threonine Kinases
;
Proto-Oncogene Proteins c-met/metabolism
;
Receptors, Transforming Growth Factor beta/genetics/metabolism
;
Recombination, Genetic
;
*Signal Transduction
;
Stomach/cytology/metabolism/pathology
;
Stomach Neoplasms/etiology/metabolism/pathology
;
Stromal Cells/*physiology
;
Transforming Growth Factor beta/*physiology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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