Related Experiment Video
Updated: Jun 22, 2026
08:49
A 3D Organotypic Melanoma Spheroid Skin Model
Published on: May 18, 2018
Functional RET G691S polymorphism in cutaneous malignant melanoma
N Narita1, A Tanemura, R Murali
1Department of Molecular Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA.
Oncogene
|June 30, 2009
Summary
The RET proto-oncogene polymorphism (RETp) is more common in desmoplastic melanomas and drives tumor progression. Glial cell line-derived neurotrophic factor (GDNF) amplifies proliferation and invasion in RETp melanoma cells.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The RET proto-oncogene encodes a receptor tyrosine kinase activated by glial cell line-derived neurotrophic factor (GDNF).
- A specific RET polymorphism (RETp) in the juxtamembrane region is a germline variant.
- Cutaneous melanomas, especially desmoplastic melanomas (DMs), exhibit neurotropic properties.
Purpose of the Study:
- To determine the frequency of RETp in cutaneous melanoma subtypes.
- To investigate the functional response of RETp-harboring melanoma cells to GDNF stimulation.
Main Methods:
- Assessed RETp frequency in 71 non-desmoplastic melanomas (non-DMs) and 70 DMs.
- Utilized melanoma cell lines with RETp, wild-type RET (RETwt), BRAF V600E mutation (BRAFmt), or wild-type BRAF (BRAFwt).
- Evaluated cell proliferation, migration, invasion, and signaling pathway activation (ERK, Akt) upon GDNF stimulation.
Main Results:
- RETp frequency was significantly higher in DMs (61%) compared to non-DMs (31%, P<0.001).
- BRAFmt was infrequent in DMs (11%).
- GDNF significantly enhanced proliferation, migration, and invasion in RETp cells, but not RETwt cells, activating ERK and Akt pathways.
Conclusions:
- RETp is a frequent germline polymorphism in cutaneous melanoma, particularly in desmoplastic subtypes.
- GDNF stimulation of RETp melanoma cells promotes tumor progression via enhanced proliferation, migration, and invasion.
- The GDNF-RETp pathway's pro-tumorigenic effects are independent of BRAFmt status.
Related Concept Videos
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:30Skin Cancer
Skin cancer is a type of cancer that occurs when there is an abnormal growth of skin cells, usually triggered by damage to the DNA within the skin cells. It is primarily caused by exposure to ultraviolet (UV) radiation from the sun or artificial sources like tanning beds. Skin cancer is the most common type of cancer worldwide, and its incidence continues to rise.
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
Basal Cell Carcinoma (BCC): BCC is the most common type of skin cancer, accounting for about 80% of cases. It typically develops in...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...