Ovarian cancer is one of the most common malignancies affecting the
female reproductive system. Granulosa cell tumours (GCT) of the ovary
arise from the granulosa cells of the ovarian follicle and produce the
hormones inhibin and estrogen.
Although they are often relatively slowly growing, late recurrences are
often fatal. It is currently not known what causes these tumours. These
studies will identify the genetic changes which lead to the development
of the cancers. To assist this molecular analysis, we use two ovarian
cell lines in culture that have many of the features of the primary
tumours including inhibin secretion.
Our group has identified abnormalities in 2 molecular pathways which
normally, in response to hormones, promote growth of granulosa cells.
Both pathways are active in the absence of normal stimuli; the cause of
this inappropriate activation is being sought.
Candidate genes, in which mutations may lie, have been targeted for
further characterisation. Other growth promoting pathways will also be
analysed. Similarly, we have evidence of genetic change leading to loss
of an inhibiting signal; this requires confirmation and full
Two drugs that are currently in clinical trials for other tumours will
be tested against the cell lines. We anticipate that identification of
the molecular events that cause GCT will enable improvements in
prognostication i.e. prediction of which tumour is prone to late
relapse and which is not. It should also help to design appropriate,
This study aims to identify the cause of a specific type of ovarian
cancer, granulosa cell tumours. Understanding the molecular causes will
aid in the development of specific treatments.