|
Comment |
Owens GE, et al reported ovulatory surges of human CG prevent hormone-induced granulosa cell tumor formation leading to the identification of
tumor-associated changes in the transcriptomes.
The authors used a
transgenic mouse model in which granulosa cell tumors occur with 100%
penetrance in CF-1 mice that harbor a novel transgene encoding a chimeric
LHbeta subunit. When this transgene is expressed in other strains of mice,
including (C57BL/6female x CF-1male,Tg) F-1 hybrids, luteomas develop even
though levels of LH remain high. This dichotomous response permits a
longitudinal comparison of global changes in transcriptomes uniquely
associated with either granulosa cell tumors or luteomas. The authors report
numerous changes in the transcriptome, including a decrease in LH receptor
mRNA and increases in several mRNAs that encode secreted proteins previously
associated with granulosa cell tumors. They identified a
constellation of mRNAs that encode proteins that may serve as new markers for
this tumor phenotype. Additional experiments indicated that periodic treatment
with human CG prevented formation of granulosa cell tumors in mice genetically
predisposed to tumor development and, instead, led to the appearance of
luteomas. More importantly, ovarian transcriptomes from the luteomas induced
by ovulatory doses of human CG permitted refined confirmation of gene
expression changes that were uniquely associated with either granulosa cell
tumors in the permissive CF-1 genetic background or in luteomas in the F-1
hybrids. Together, these dynamic changes in the ovarian transcriptome indict
various signaling pathways potentially involved in mediating the actions of LH
over time and, depending on genetic background, the formation of either a
luteoma or a granulosa cell tumor. Frizzled 10
is a gene that is up regulated in granulosa cell tumors.
|