The ERK Signaling Cascade Inhibits Gonadotropin-Stimulated Steroidogenesis.

The response of granulosa cells to Luteinizing Hormone (LH) and Follicle- Stimulating Hormone (FSH) is mediated mainly by cAMP/protein kinase A (PKA) signaling. Notably, the activity of the extracellular signal-regulated kinase (ERK) signaling cascade is elevated in response to these stimuli as well. We studied the involvement of the ERK cascade in LH- and FSH-induced steroidogenesis in two granulosa-derived cell lines, rLHR-4 and rFSHR-17, respectively.

MITF deficiency and oncogenic GNAQ each promote proliferation programs in zebrafish melanocyte lineage cells.

Uveal melanoma (UM) is the most common primary malignancy of the adult eye but lacks any FDA-approved therapy for the deadly metastatic disease. Thus, there is a great need to dissect the driving mechanisms for UM and develop strategies to evaluate potential therapeutics. Using an autochthonous zebrafish model, we previously identified MITF, the master melanocyte transcription factor, as a tumor suppressor in GNAQ -driven UM.

MITF deficiency accelerates GNAQ-driven uveal melanoma.

Cutaneous melanoma (CM) and uveal melanoma (UM) both originate from the melanocytic lineage but are primarily driven by distinct oncogenic drivers, BRAF/NRAS or GNAQ/GNA11, respectively. The melanocytic master transcriptional regulator, MITF, is essential for both CM development and maintenance, but its role in UM is largely unexplored. Here, we use zebrafish models to dissect the key UM oncogenic signaling events and establish the role of MITF in UM tumors.

Uveal melanoma driver mutations in GNAQ/11 yield numerous changes in melanocyte biology.

Uveal melanoma (UM) is the most common primary intraocular cancer and has a high incidence of metastasis, which lacks any effective treatment. Here, we present zebrafish models of UM, which are driven by melanocyte-specific expression of activating GNAQ or GNA11 alleles, GNAQ/11 , the predominant initiating mutations for human UM. When combined with mutant tp53, GNAQ/11 transgenics develop various melanocytic tumors, including UM, with near complete penetrance.