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Testosterone regulates cell proliferation in aggressive fibromatosis (desmoid tumour).

Hong H, Nadesan P, Poon R, Alman BA - Br. J. Cancer (2011)

Bottom Line: Aggressive fibromatosis (desmoid tumour) is a locally invasive tumour caused by mutations resulting in β-catenin protein stabilisation.Testosterone regulates β-catenin protein level and proliferation rate in this mesenchymal tumour.This work identifies the therapeutic use of testosterone blockade in aggressive fibromatosis as an area for further investigation.

View Article: PubMed Central - PubMed

Affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto Medical Discovery Tower, 101 College Street, Toronto, ON, Canada M5G 1L7.

ABSTRACT

Background: Aggressive fibromatosis (desmoid tumour) is a locally invasive tumour caused by mutations resulting in β-catenin protein stabilisation. Apc1638N mice are predisposed to developing aggressive fibromatosis tumours, and male mice develop greater numbers of tumours than female mice, suggesting a role for androgens in this tumour type.

Methods: Human aggressive fibromatosis tumours were examined for the expression of the androgen receptor, and primary human tumour cell cultures were treated with testosterone. Orchidectomised Apc1638N mice were investigated for the development of tumours, and were treated with testosterone to study the effect of tumour formation and the level of β-catenin.

Results: Androgen receptors are universally expressed in human aggressive fibromatosis tumours. Testosterone increased the proliferation rate and β-catenin protein level in a dose-dependent manner in human aggressive fibromatosis tumours. Orchiectomy reduced the number and size of tumours that formed in male Apc1638N mice to a similar level as observed in female mice. Testosterone treatment increased the number of tumours that formed in orchidectomised male mice, and resulted in a marked increase in β-catenin protein levels.

Conclusion: Testosterone regulates β-catenin protein level and proliferation rate in this mesenchymal tumour. This work identifies the therapeutic use of testosterone blockade in aggressive fibromatosis as an area for further investigation.

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Related in: MedlinePlus

Testosterone regulates the size and number of aggressive fibromatosis tumours in castrated mice. The number and volume of aggressive fibromatosis tumours in 5-month-old Apc1638N mice. Volume is given as mean mm3 per individual tumour. Testosterone treatment brings the number and volume of tumours that develop close to that of mice that are not castrated. Data are given as means and 95% confidence intervals for different concentrations of testosterone. An asterisk above data shows a significant difference from castrated male mice.
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fig4: Testosterone regulates the size and number of aggressive fibromatosis tumours in castrated mice. The number and volume of aggressive fibromatosis tumours in 5-month-old Apc1638N mice. Volume is given as mean mm3 per individual tumour. Testosterone treatment brings the number and volume of tumours that develop close to that of mice that are not castrated. Data are given as means and 95% confidence intervals for different concentrations of testosterone. An asterisk above data shows a significant difference from castrated male mice.

Mentions: There are a number of factors that are altered with castration, and to determine whether testosterone is a major factor contributing to the development of aggressive fibromatosis, castrated male Apc1638N mice were administered testosterone to restore serum levels comparable to that of control mice. We found that treatment with 50 μg per g of body weight of testosterone resulted in a significant increase in the number of tumours that formed, close to that of uncastrated mice (Figure 4). An additional cohort of mice were castrated and treated with a carrier, and there was no significant difference in the number of tumours that formed compared with castrated mice alone (6.63±2.16 vs 8.63±2.25). The average volume per tumour in orchidectomised Apc1638N mice treated with testosterone was larger than those treated with carrier (Figure 4), and the average tumour volume in castrated mice was close to that in female mice (4.14±2.57 vs 4.15±2.08 mm3). Castrated mice treated with 20 μg per g of body weight of testosterone developed a number and volume of tumours intermediate between the other groups. Plasma testosterone levels were 398±95 pg ml−1 (mean±95% confidence interval) in control mice, 6±6 pg ml−1 in castrated mice, 362±64 in mice treated with 50 μg per g of body weight of testosterone and 178±59 pg ml−1 in mice treated with 20 μg per g of body weight of testosterone. There was a significant difference in levels between castrated mice and mice treated with 20 μg per g of body weight of testosterone compared with control mice (P<0.05), but there was no significant difference between mice treated with 50 μg per g of body weight of testosterone and control mice. This data show that the effect of castration in the aggressive fibromatosis phenotype can be rescued by testosterone.


Testosterone regulates cell proliferation in aggressive fibromatosis (desmoid tumour).

Hong H, Nadesan P, Poon R, Alman BA - Br. J. Cancer (2011)

Testosterone regulates the size and number of aggressive fibromatosis tumours in castrated mice. The number and volume of aggressive fibromatosis tumours in 5-month-old Apc1638N mice. Volume is given as mean mm3 per individual tumour. Testosterone treatment brings the number and volume of tumours that develop close to that of mice that are not castrated. Data are given as means and 95% confidence intervals for different concentrations of testosterone. An asterisk above data shows a significant difference from castrated male mice.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3101926&req=5

fig4: Testosterone regulates the size and number of aggressive fibromatosis tumours in castrated mice. The number and volume of aggressive fibromatosis tumours in 5-month-old Apc1638N mice. Volume is given as mean mm3 per individual tumour. Testosterone treatment brings the number and volume of tumours that develop close to that of mice that are not castrated. Data are given as means and 95% confidence intervals for different concentrations of testosterone. An asterisk above data shows a significant difference from castrated male mice.
Mentions: There are a number of factors that are altered with castration, and to determine whether testosterone is a major factor contributing to the development of aggressive fibromatosis, castrated male Apc1638N mice were administered testosterone to restore serum levels comparable to that of control mice. We found that treatment with 50 μg per g of body weight of testosterone resulted in a significant increase in the number of tumours that formed, close to that of uncastrated mice (Figure 4). An additional cohort of mice were castrated and treated with a carrier, and there was no significant difference in the number of tumours that formed compared with castrated mice alone (6.63±2.16 vs 8.63±2.25). The average volume per tumour in orchidectomised Apc1638N mice treated with testosterone was larger than those treated with carrier (Figure 4), and the average tumour volume in castrated mice was close to that in female mice (4.14±2.57 vs 4.15±2.08 mm3). Castrated mice treated with 20 μg per g of body weight of testosterone developed a number and volume of tumours intermediate between the other groups. Plasma testosterone levels were 398±95 pg ml−1 (mean±95% confidence interval) in control mice, 6±6 pg ml−1 in castrated mice, 362±64 in mice treated with 50 μg per g of body weight of testosterone and 178±59 pg ml−1 in mice treated with 20 μg per g of body weight of testosterone. There was a significant difference in levels between castrated mice and mice treated with 20 μg per g of body weight of testosterone compared with control mice (P<0.05), but there was no significant difference between mice treated with 50 μg per g of body weight of testosterone and control mice. This data show that the effect of castration in the aggressive fibromatosis phenotype can be rescued by testosterone.

Bottom Line: Aggressive fibromatosis (desmoid tumour) is a locally invasive tumour caused by mutations resulting in β-catenin protein stabilisation.Testosterone regulates β-catenin protein level and proliferation rate in this mesenchymal tumour.This work identifies the therapeutic use of testosterone blockade in aggressive fibromatosis as an area for further investigation.

View Article: PubMed Central - PubMed

Affiliation: Program in Developmental and Stem Cell Biology, Hospital for Sick Children, Toronto Medical Discovery Tower, 101 College Street, Toronto, ON, Canada M5G 1L7.

ABSTRACT

Background: Aggressive fibromatosis (desmoid tumour) is a locally invasive tumour caused by mutations resulting in β-catenin protein stabilisation. Apc1638N mice are predisposed to developing aggressive fibromatosis tumours, and male mice develop greater numbers of tumours than female mice, suggesting a role for androgens in this tumour type.

Methods: Human aggressive fibromatosis tumours were examined for the expression of the androgen receptor, and primary human tumour cell cultures were treated with testosterone. Orchidectomised Apc1638N mice were investigated for the development of tumours, and were treated with testosterone to study the effect of tumour formation and the level of β-catenin.

Results: Androgen receptors are universally expressed in human aggressive fibromatosis tumours. Testosterone increased the proliferation rate and β-catenin protein level in a dose-dependent manner in human aggressive fibromatosis tumours. Orchiectomy reduced the number and size of tumours that formed in male Apc1638N mice to a similar level as observed in female mice. Testosterone treatment increased the number of tumours that formed in orchidectomised male mice, and resulted in a marked increase in β-catenin protein levels.

Conclusion: Testosterone regulates β-catenin protein level and proliferation rate in this mesenchymal tumour. This work identifies the therapeutic use of testosterone blockade in aggressive fibromatosis as an area for further investigation.

Show MeSH
Related in: MedlinePlus