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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

Fewer and smaller aggressive fibromatosis tumours develop in castrated Apc1638N mice. The number and volume of aggressive fibromatosis tumours in 5-month-old Apc1638N mice. Volume is given as mean mm3 per individual tumour. Castrated mice develop a similar number of tumours as female mice that are also of a similar volume. Data are given as means and 95% confidence intervals. An asterisk above data shows a significant difference from castrated male mice.
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fig3: Fewer and smaller aggressive fibromatosis tumours develop in castrated Apc1638N mice. The number and volume of aggressive fibromatosis tumours in 5-month-old Apc1638N mice. Volume is given as mean mm3 per individual tumour. Castrated mice develop a similar number of tumours as female mice that are also of a similar volume. Data are given as means and 95% confidence intervals. An asterisk above data shows a significant difference from castrated male mice.

Mentions: To examine the role of testosterone in vivo, we examined castrated male Apc1638N mice and compared the tumour phenotype to animals that had undergone a sham operation, and to female mice. The number and size of tumours that developed in 5-month-old castrated Apc1638N mice was significantly reduced and smaller in volume as compared with sham non-castrated mice (Figure 3). Interestingly, the number and size of tumours that developed in male castrated mice is similar to the number that developed in female mice (8.63±2.25 vs 6.23±2.96 average number of tumours). In contrast, there was no significant difference in the number of gastrointestinal polyps that developed in these mice between the two groups. This data suggest an in vivo role for androgens in aggressive fibromatosis.


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

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

Fewer and smaller aggressive fibromatosis tumours develop in castrated Apc1638N mice. The number and volume of aggressive fibromatosis tumours in 5-month-old Apc1638N mice. Volume is given as mean mm3 per individual tumour. Castrated mice develop a similar number of tumours as female mice that are also of a similar volume. Data are given as means and 95% confidence intervals. An asterisk above data shows a significant difference from castrated male mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3101926&req=5

fig3: Fewer and smaller aggressive fibromatosis tumours develop in castrated Apc1638N mice. The number and volume of aggressive fibromatosis tumours in 5-month-old Apc1638N mice. Volume is given as mean mm3 per individual tumour. Castrated mice develop a similar number of tumours as female mice that are also of a similar volume. Data are given as means and 95% confidence intervals. An asterisk above data shows a significant difference from castrated male mice.
Mentions: To examine the role of testosterone in vivo, we examined castrated male Apc1638N mice and compared the tumour phenotype to animals that had undergone a sham operation, and to female mice. The number and size of tumours that developed in 5-month-old castrated Apc1638N mice was significantly reduced and smaller in volume as compared with sham non-castrated mice (Figure 3). Interestingly, the number and size of tumours that developed in male castrated mice is similar to the number that developed in female mice (8.63±2.25 vs 6.23±2.96 average number of tumours). In contrast, there was no significant difference in the number of gastrointestinal polyps that developed in these mice between the two groups. This data suggest an in vivo role for androgens in aggressive fibromatosis.

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