MYC is not detected in highly proliferating normal spermatogonia but is coupled with CIP2A in testicular cancers
Ventelä S; Toppari J; Westermarck J; Mäkelä J-A; Sears RC
https://urn.fi/URN:NBN:fi-fe2021042715496
Tiivistelmä
High MYC expression is linked to proliferative activity in most normal
tissues and in cancer. MYC also supports self-renewal and proliferation
of many types of tissue progenitor cells. Cancerous inhibitor of PP2A
(CIP2A) promotes MYC phosphorylation and activity during intestinal
crypt regeneration in vivo and in various cancers. CIP2A also supports male germ cell proliferation in vivo.
However, the role of MYC in normal germ cell proliferation and
spermatogonial progenitor self-renewal is currently unclear. Here, we
demonstrate that male germ cells are CIP2A-positive but lack detectable
levels of MYC protein; whereas MYC is highly expressed in Leydig cells
and peritubular myoid cells contributing thereby to the testicular stem
cell niche. On the other hand, MYC was co-expressed with CIP2A in
testicular cancers. These results demonstrate that CIP2A and MYC are
spatially uncoupled in the regulation of spermatogenesis, but functional
relationship between these two human oncoproteins is established during
testicular cancer transformation. We propose that further analysis of
mechanisms of MYC silencing in spermatogonial progenitors may reveal
novel fundamental information relevant to understanding of MYC
expression in cancer.
Kokoelmat
- Rinnakkaistallenteet [19207]