Περίληψη:
Recent evidence indicates that growth hormone-releasing hormone (GHRH)
functions as an autocrine/paracrine growth factor for various human
cancers. A splice variant (SV) of the full-length receptor for GHRH
(GHRHR) is widely expressed in various primary human cancers and
established cancer cell lines and appears to mediate the proliferative
effects of GHRH. To investigate in greater detail the role of SV1 in
tumorigenesis, we have expressed the full-length GHRHR and its SV1 in
MCF-7 human breast cancer cells that do not possess either GHRHR or SV1.
In accordance with previous findings, the expression of both GHRHR and
SV1 restored the sensitivity to GHRH-induced stimulation of cell
proliferation, with SV1 being more potent than the GHRHR. Furthermore,
MCF-7 cells transfected with SV1 proliferated more quickly than the
controls, even in the absence of exogenously added GHRH, suggesting the
existence of intrinsic, ligand-independent activity of SV1 after its
transfection. In agreement with the stimulation of cell proliferation,
the levels of proliferation markers cyclin D1, cyclin E, and
proliferating cell nuclear antigen were elevated in MCF-7 cells treated
with GHRH, cultured in both serum-free and serum-containing media. In
addition, SV1 caused a considerable stimulation of the ability of MCF-7
cells to grow in semisolid medium, an assay considered diagnostic for
cell transformation. Collectively, our findings show that the expression
of SV1 confers oncogenic activity and provide further evidence that GHRH
operates as a growth factor in breast cancer and probably other cancers
as well.
Συγγραφείς:
Barabutis, Nektarios
Tsellou, Erasmia
Schally, Andrew V. and
Kouloheri, Stavroula
Kalofoutis, Anastasios
Kiaris, Hippokratis
