GH Signaling in Human Melanoma Cell Lines

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 88-108-GHRH, GH & IGF Biology & Signaling
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-95
Ashiya Buckels*, Yue Zhang, Jing Jiang, Farrukh Afaq, Mohammad Athar and Stuart Jonathan Frank
University of Alabama at Birmingham, Birmingham, AL
Growth hormone (GH) transmits somatogenic and metabolic effects by interacting with the cell surface GH receptor (GHR) and activating JAK2, STAT5, and other pathways. Recent data in humans with GHR deficiency and GH insensitivity syndrome, as well as experimental evidence in rodent models of GH or GHR deficiency suggest that development of cancers (particularly breast and prostate cancers) is diminished with disrupted GH-GHR signaling. GHR is expressed in various tissues, including in the skin. In particular, GHR expression and/or effects of GH on behavior have been noted in melanocytes and GHR expression is enriched in human melanoma isolates. As melanoma is a particularly aggressive and treatment-resistant human cancer, we have embarked on characterization of GH signaling and GHR structure and function in human melanoma. To date, we have tested six individual human melanoma cell lines that have also been previously characterized to some degree for their expression of oncogenes and other attributes. Using our anti-GHR and anti-JAK2 antibodies, as well as other immunochemical reagents, we specifically detect GHR protein in three of the six lines studied to date. Two of these three GHR-positive cell lines express the activating B-Raf (V600E) oncogene and the third bears an activating mutant form (Q61R) of N-Ras. In each of the lines in which GHR was immunologically detected, treatment with GH elicited acute and transient tyrosine phosphorylation of GHR, JAK2, and STAT5, with STAT5 phosphorylation persisting for at least 30 minutes and in each case appearing later and lasting longer than both GHR and JAK2 phosphorylation. Notably, GH treatment also rapidly downregulated GHR abundance, as would be expected after initiation of signaling. In each of the three GHR-positive cell lines, ERK was basally tyrosine phosphorylated, as anticipated with oncogenically-driven constitutive activation of upstream ERK pathway activators (Ras and Raf). GH treatment did not appreciably change the level of ERK phosphorylation in any of the melanoma cell lines. Testing of other human melanoma cell lines, as well as further characterization of biological effects of GH on the GHR-positive lines, are underway. We believe that our observations of GH signaling in human melanoma isolates may identify new cellular models of GH action and potentially have translational significance.

Nothing to Disclose: AB, YZ, JJ, FA, MA, SJF

*Please take note of The Endocrine Society's News Embargo Policy at

Sources of Research Support: NIH R01 DK46395 (to SJF)