cd44 deletion suppresses atypia in the precancerous mouse testis.
Mol Carcinog
; 58(5): 621-626, 2019 05.
Article
in En
| MEDLINE
| ID: mdl-30582228
ABSTRACT
Loss-of-function of RHAMM causes hypofertility and testicular atrophy in young mice, followed by germ cell neoplasia in situ (GCNIS) of the testis, cellular atypia, and development of the testicular germ cell tumor (TGCT) seminoma. These pathologies reflect the risk factors and phenotypes that precede seminoma development in humans and-given the high prevalence of RHAMM downregulation in human seminoma-link RHAMM dysfunction with the aetiology of male hypofertility and GCNIS-related TGCTs. The initiating event underlying these pathologies, in RHAMM mutant testis, is premature displacement of undifferentiated progenitors from the basal compartment. We hypothesized that cd44 (both cancer initiating cell- and oncogenic progression marker) will drive GCNIS development, induced by RHAMM-loss-of-function in the mouse. We report that cd44 is expressed in a specific subset of GCNIS testes. Its genetic deletion has no effect on GCNIS onset, but it ameliorates oncogenic progression. We conclude that cd44 expression, combined with RHAMM dysfunction, promotes oncogenic progression in the testis.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Precancerous Conditions
/
Testicular Neoplasms
/
Carcinoma in Situ
/
Extracellular Matrix Proteins
/
Neoplasms, Germ Cell and Embryonal
/
Hyaluronan Receptors
/
Infertility, Male
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Mol Carcinog
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2019
Document type:
Article
Affiliation country: