Transforming growth factor-beta expression in mouse lung carcinogenesis.
Transforming growth factor-beta (TGF-beta) is a multifunctional growth modulator that inhibits the proliferation of many epithelial cells while stimulating the proliferation of most fibroblasts. To examine the role of TGF-beta in mouse lung chemically induced tumorigenesis, expression of the TGF-beta 1, -beta 2, and -beta 3 proteins was examined in A/J mice treated with the carcinogen urethane to induce lung adenomas using immunohistochemical staining analysis. Immunostaining for the TGF-beta ligands was detected in the epithelium of the bronchioles of untreated A/J mice with immunostaining being more intense for TGF-beta 1 than for TGF-beta 2 and TGF-beta 3; immunostaining for each TGF-beta ligand was also detected in the bronchiolar epithelium of urethane-treated A/J mice at levels similar to untreated mice. Immunostaining for the TGF-beta ligands was also detected in adenomas by 2 months; staining for TGF-beta 1, -beta 2, and -beta 3 in adenomas was detected at levels comparable with bronchioles. Following treatment with urethane for 8 months, immunostaining for TGF-beta s 1, 2, and 3 in bronchioles persisted at levels comparable to that in normal bronchioles and also persisted in adenomas, with staining for the TGF-beta ligands being very prominent on the edge of the tumor. Expression of TGF-beta 1 mRNA was examined in urethane-treated mouse lung tissue using Northern blot hybridization; here, expression of TGF-beta 1 mRNA increased 2-fold in 3-month urethane-treated lung tissue and an additional 2.5-fold by 8 months following urethane administration. Expression of TGF-beta 1 mRNA was also examined in nontumorigenic and tumorigenic mouse lung cells; in these cells, expression of TGF-beta 1 mRNA was higher in the tumorigenic cells than in the nontumorigenic cell line. These data show that there is an increase in expression of TGF-beta 1 during tumorigenesis and suggest that TGF-beta may play an important role in mouse lung carcinogenesis induced by urethane.
Jakowlew
S B
SB
National Cancer Institute, Medicine Branch, Rockville, Maryland, USA.
Moody
T W
TW
You
L
L
Mariano
J M
JM
D000236:Adenoma / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015152:Blotting, Northern; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D007124:Immunoenzyme Techniques; D008024:Ligands; D008168:Lung / Q000166:cytology / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014520:Urethane / Q000633:toxicity
D002273:Carcinogens; D017931:DNA Primers; D008024:Ligands; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014520:Urethane