JARID1B expression in human melanoma and benign melanocytic skin lesions

Abstract

It has been suggested that dynamically regulated expression of the JARID1B protein is required for the continuous growth of tumors and at the same time downregulated in melanoma. The majority of the data on a role of JARID1B in maintaining tumor growth has come from in-vitro and xenografting experiments, with only one immunohistochemical study involving human tissues. We compared JARID1B expression levels in human melanomas and benign nevi and analyzed patterns of spatial distributions of positive cells among different skin layers of the lesions. The expression of JARID1B was evaluated by immunohistochemistry in formalin-fixed paraffin-embedded samples of 30 nevi, 27 primary melanomas, four lymph node metastases, and one local recurrence of melanoma. Staining for JARID1B protein was stronger in melanomas compared with nevi. We also found a significant difference in the spatial distribution of positive cells in individual skin layers of nevi and melanomas. Staining of melanocytes located in granular and spinous layers of nevi was observed very rarely, whereas for melanomas, the mean percentage fractions of positive cells present in these layers exceeded the maximum values found for nevi. The spatial patterns and expression levels of JARID1B did not change significantly with melanoma progression and were similar for primary, metastatic, and recurrent melanomas. Contrary to earlier reports, this study shows enhanced expression of JARID1B by melanoma cells and indicates that such an enhancement may be an early event in the disease progression, is not correlated with melanoma invasiveness, and therefore may not be a suitable candidate as a prognostic marker.

Identification of new genes associated with melanoma

“…Among the 167 genes that were up‐regulated in PM compared to MN, we found a high overlap with previously reported genes, e.g. PRAME, SSP1 (13,14), CXCL9, PHACTR1, CITED‐1, BCL2A1 (13,15) S100A9, MMP1, FN1 (16), NNMT, SERPIN A3 (13), MCAM (17), ISG15 (18), CDK‐2, and CDK‐4 (19), GDF15 (13,15,20) and Hey1 (15,16). Comparing genes that were down‐regulated from PM to MN with previous studies, we found consensus for CIRBP, FEZ1, PPP1R3C, LDOC1, TRPM1 (16), Desmoglein (17), KRT‐15 (13), FABP7 (20), p57KIP2 and CDKN1 (21).…”

JARID1B promotes metastasis and epithelial-mesenchymal transition via PTEN/AKT signaling in hepatocellular carcinoma cells

“…The putative role of JARID1B as an oncogene in cancer development is supported by the observations that JARID1B is highly expressed in prostate cancer and other malignant tumors relative to normal tissues [ 12 , 23 , 32 , 13 ]. The fact that JARID1B as a demethylase capable of removing three methyl groups from histone H3 lysine 4, subsequently downregulation several well-known tumor suppressor genes [ 27 , 33 , 34 ].…”

Melanocytic nevi and melanoma: unraveling a complex relationship

“…JARID1B ( KDM5B ) is expressed at higher levels in melanoma than nevi, 143 and has been shown to be required for continuous growth of melanoma in experimental models. 144,145 SETDB1 is a methyltransferase responsible for H3K9me3 methylation (as seen in SAHF) that interestingly has actually been shown to be recurrently amplified in melanoma.…”