Androgen and Androgen Receptor in Kidney Cancer
In contrast to the results of current epidemiological study, hormonal therapy had
been evaluated in clinical trials for RCC patients in early decades.
Despite the discovery of the therapeutic effects of both progesterone
and androgen in RCC patients, their therapeutic outcomes had not been appreciated.
Since androgen and AR are involved in male-gender associated diseases,
recent studies have switched the focus to target androgen and AR signaling in RCC.
It was first disclosed that high AR expression is correlated with poor prognosis for
RCC patients; signifying shorter overall survival, relapse-free survival, and cancer-specific
survival.
However, another study suggests that AR is actually expressed in more than 90% of
normal kidney human samples and that there are no differential AR expressions in normal male
and female kidneys.
In addition, AR expression levels are inversely correlated with pT Stage
and Fuhrman’s Grade in RCC patients. This surprising result leads to further investigation of
the transactivation activity of AR, as AR mainly exerts its function through transcriptional
regulation of target genes.
Androgen treatment does not promote the transactivation activity
of AR in commonly used RCC cell lines, such as CAKI-2 and OSRC-2, although AR expression
could be detected in these cells. These interesting results bring up novel questions.
How does male gender predispose RCC development if AR expression is reduced in RCC samples? Can
AR be the therapeutic target even if RCC has AR expression without transactivation activity.
Androgen and Androgen Receptor in Kidney Cancer
Nephrol Open J. 2015; 1(2): e7-e8. doi: 10.17140/NPOJ-1-e003