Limits...
Overexpression of FGF9 in prostate epithelial cells augments reactive stroma formation and promotes prostate cancer progression.

Huang Y, Jin C, Hamana T, Liu J, Wang C, An L, McKeehan WL, Wang F - Int. J. Biol. Sci. (2015)

Bottom Line: Both in vivo and in vitro data indicated that FGF9 promoted TGFβ1 expression via increasing cJun-mediated signaling.Moreover, in silico analyses showed that the expression level of FGF9 was positively associated with expression of TGFβ1 and its downstream signaling molecules in human prostate cancers.Collectively, our data demonstrated that overexpressing FGF9 in PCa cells augmented the formation of reactive stroma and promoted PCa initiation and progression.

View Article: PubMed Central - PubMed

Affiliation: 1. Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USA.

ABSTRACT
Bone metastasis is the major cause of morbidity and mortality of prostate cancer (PCa). Fibroblast growth factor 9 (FGF9) has been reported to promote PCa bone metastasis. However, the mechanism by which overexpression of FGF9 promotes PCa progression and metastasis is still unknown. Herein, we report that transgenic mice forced to express FGF9 in prostate epithelial cells (F9TG) developed high grade prostatic intraepithelial neoplasia (PIN) in an expression level- and time-dependent manner. Moreover, FGF9/TRAMP bigenic mice (F9TRAMP) grew advanced PCa earlier and had higher frequencies of metastasis than TRAMP littermates. We observed tumor microenvironmental changes including hypercellularity and hyperproliferation in the stromal compartment of F9TG and F9TRAMP mice. Expression of TGFβ1, a key signaling molecule overexpressed in reactive stroma, was increased in F9TG and F9TRAMP prostates. Both in vivo and in vitro data indicated that FGF9 promoted TGFβ1 expression via increasing cJun-mediated signaling. Moreover, in silico analyses showed that the expression level of FGF9 was positively associated with expression of TGFβ1 and its downstream signaling molecules in human prostate cancers. Collectively, our data demonstrated that overexpressing FGF9 in PCa cells augmented the formation of reactive stroma and promoted PCa initiation and progression.

No MeSH data available.


Related in: MedlinePlus

Overexpression of FGF9 in prostatic epithelial cells promotes PCa progression in mice. A.In situ hybridization showing expression of Fgf9 mRNA in mouse prostates. B. Real-time RT-PCR analyses of Fgf9 expression in TRAMP and F9TRAMP prostates at 4 months. C. Statistical analysis of prostate/body weight ratio of TRAMP and F9TRAMP prostates at the ages of 4, 5, and 6 months. D. H&E staining of TRAMP and F9TRAMP prostates at the ages of 3, 4, and 6 months. E. Quantitative analyses of prostate lesions of TRAMP and F9TRAMP mice at the age of 3 or 6 months. N=5 per group. F. Immunostaining comparing AR, P63, and Ki67 expression in TRAMP and F9TRAMP prostates. Panel g, statistical analyses of proliferating cells in TRAMP and F9TRAMP prostates at the indicated ages. Scale bars, 50 µm
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4495412&req=5

Figure 3: Overexpression of FGF9 in prostatic epithelial cells promotes PCa progression in mice. A.In situ hybridization showing expression of Fgf9 mRNA in mouse prostates. B. Real-time RT-PCR analyses of Fgf9 expression in TRAMP and F9TRAMP prostates at 4 months. C. Statistical analysis of prostate/body weight ratio of TRAMP and F9TRAMP prostates at the ages of 4, 5, and 6 months. D. H&E staining of TRAMP and F9TRAMP prostates at the ages of 3, 4, and 6 months. E. Quantitative analyses of prostate lesions of TRAMP and F9TRAMP mice at the age of 3 or 6 months. N=5 per group. F. Immunostaining comparing AR, P63, and Ki67 expression in TRAMP and F9TRAMP prostates. Panel g, statistical analyses of proliferating cells in TRAMP and F9TRAMP prostates at the indicated ages. Scale bars, 50 µm

Mentions: To determine whether overexpression of FGF9 contributed to initiation and progression of PCa, F9TG mice were crossed with TRAMP mice to generate FGF9/TRAMP bigenic mice (hereafter designated as F9TRAMP). In situ hybridization (Fig. 3A) and real-time RT-PCR (Fig. 3B) analyses revealed that FGF9 was highly expressed in the epithelium of the F9TRAMP prostate. F9TRAMP mice had a median survival time of 218 days, which was shorter than that of TRAMP mice that had a median survival time of 234 days. Although similar at early ages, the average weight of F9TRAMP prostates (n=13) was heavier than that of TRAMP prostates (n=10) at the age of 6 months or older (Fig. 3C).


Overexpression of FGF9 in prostate epithelial cells augments reactive stroma formation and promotes prostate cancer progression.

Huang Y, Jin C, Hamana T, Liu J, Wang C, An L, McKeehan WL, Wang F - Int. J. Biol. Sci. (2015)

Overexpression of FGF9 in prostatic epithelial cells promotes PCa progression in mice. A.In situ hybridization showing expression of Fgf9 mRNA in mouse prostates. B. Real-time RT-PCR analyses of Fgf9 expression in TRAMP and F9TRAMP prostates at 4 months. C. Statistical analysis of prostate/body weight ratio of TRAMP and F9TRAMP prostates at the ages of 4, 5, and 6 months. D. H&E staining of TRAMP and F9TRAMP prostates at the ages of 3, 4, and 6 months. E. Quantitative analyses of prostate lesions of TRAMP and F9TRAMP mice at the age of 3 or 6 months. N=5 per group. F. Immunostaining comparing AR, P63, and Ki67 expression in TRAMP and F9TRAMP prostates. Panel g, statistical analyses of proliferating cells in TRAMP and F9TRAMP prostates at the indicated ages. Scale bars, 50 µm
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4495412&req=5

Figure 3: Overexpression of FGF9 in prostatic epithelial cells promotes PCa progression in mice. A.In situ hybridization showing expression of Fgf9 mRNA in mouse prostates. B. Real-time RT-PCR analyses of Fgf9 expression in TRAMP and F9TRAMP prostates at 4 months. C. Statistical analysis of prostate/body weight ratio of TRAMP and F9TRAMP prostates at the ages of 4, 5, and 6 months. D. H&E staining of TRAMP and F9TRAMP prostates at the ages of 3, 4, and 6 months. E. Quantitative analyses of prostate lesions of TRAMP and F9TRAMP mice at the age of 3 or 6 months. N=5 per group. F. Immunostaining comparing AR, P63, and Ki67 expression in TRAMP and F9TRAMP prostates. Panel g, statistical analyses of proliferating cells in TRAMP and F9TRAMP prostates at the indicated ages. Scale bars, 50 µm
Mentions: To determine whether overexpression of FGF9 contributed to initiation and progression of PCa, F9TG mice were crossed with TRAMP mice to generate FGF9/TRAMP bigenic mice (hereafter designated as F9TRAMP). In situ hybridization (Fig. 3A) and real-time RT-PCR (Fig. 3B) analyses revealed that FGF9 was highly expressed in the epithelium of the F9TRAMP prostate. F9TRAMP mice had a median survival time of 218 days, which was shorter than that of TRAMP mice that had a median survival time of 234 days. Although similar at early ages, the average weight of F9TRAMP prostates (n=13) was heavier than that of TRAMP prostates (n=10) at the age of 6 months or older (Fig. 3C).

Bottom Line: Both in vivo and in vitro data indicated that FGF9 promoted TGFβ1 expression via increasing cJun-mediated signaling.Moreover, in silico analyses showed that the expression level of FGF9 was positively associated with expression of TGFβ1 and its downstream signaling molecules in human prostate cancers.Collectively, our data demonstrated that overexpressing FGF9 in PCa cells augmented the formation of reactive stroma and promoted PCa initiation and progression.

View Article: PubMed Central - PubMed

Affiliation: 1. Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, USA.

ABSTRACT
Bone metastasis is the major cause of morbidity and mortality of prostate cancer (PCa). Fibroblast growth factor 9 (FGF9) has been reported to promote PCa bone metastasis. However, the mechanism by which overexpression of FGF9 promotes PCa progression and metastasis is still unknown. Herein, we report that transgenic mice forced to express FGF9 in prostate epithelial cells (F9TG) developed high grade prostatic intraepithelial neoplasia (PIN) in an expression level- and time-dependent manner. Moreover, FGF9/TRAMP bigenic mice (F9TRAMP) grew advanced PCa earlier and had higher frequencies of metastasis than TRAMP littermates. We observed tumor microenvironmental changes including hypercellularity and hyperproliferation in the stromal compartment of F9TG and F9TRAMP mice. Expression of TGFβ1, a key signaling molecule overexpressed in reactive stroma, was increased in F9TG and F9TRAMP prostates. Both in vivo and in vitro data indicated that FGF9 promoted TGFβ1 expression via increasing cJun-mediated signaling. Moreover, in silico analyses showed that the expression level of FGF9 was positively associated with expression of TGFβ1 and its downstream signaling molecules in human prostate cancers. Collectively, our data demonstrated that overexpressing FGF9 in PCa cells augmented the formation of reactive stroma and promoted PCa initiation and progression.

No MeSH data available.


Related in: MedlinePlus