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Growth Hormone Receptor in Melanoma: A Unique Approach to Therapy

Basu, Reetobrata
http://orcid.org/0000-0001-8415-1356
http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1470923234

Abstract Details

2016, Doctor of Philosophy (PhD), Ohio University, Molecular and Cellular Biology (Arts and Sciences).
Human melanomas are one of the most therapy resistant types of cancer, expressing a repertoire of mechanisms for drug resistance. Intracellular signaling networks used by the melanoma cells for active proliferation, migration, invasion, therapy resistance and metastases happen to strongly overlap with those regulated by the human growth hormone (hGH). Indeed consistently high levels of GH receptor (GHR) expression have been observed in almost all melanoma cell lines in the NCI60 human cancer panel. There are no comprehensive studies investigating the effects of GH action or GHR antagonism on the GH-responsive intracellular signaling pathways and downstream effects in human melanoma. Here we report for the first time, a detailed analysis of the effect of siRNA mediated GHR knock-down (KD) and effect of hGH on the intracellular signaling and downstream phenotypes in human melanoma cells. We report the existence of an autocrine loop of hGH-GHR in the aforesaid human melanoma cell lines, changes observed in relevant intracellular signaling pathways, RNA transcript level changes observed in multiple key modulators of the GH/GHR axis. Phosphorylation states of the JAK2, SRC, STAT1, 3, and 5, p44/42-MAPK, AKT and mTOR increased in a dose-dependent manner with hGH stimulation and were significantly attenuated by GHR-KD. Differential yet significant changes were observed in the relative mRNA transcript levels of prolactin (PRL), insulin and related growth factors (IGF1, IGF2) and their receptors, following hGH treatment or GHR-KD. Thus, the GH/GHR interaction can influence the levels of the JAK2, SRC, STAT1, 3, and 5, p44/42-MAPK, AKT and mTOR in human melanoma cells and may provide leads as to potential targets for therapeutic intervention.
Shiyong Wu (Advisor)
John Kopchick (Committee Member)
185 p.
Biochemistry; Biology; Endocrinology; Molecular Biology; Oncology
melanoma; growth hormone; growth hormone receptor; drug resistance; GH; GHR; cancer; drug resistance; melanogenesis; MITF; EMT; ABC transporters; RNAi; chemotherapy

Recommended Citations

Citations

  • Basu, R. (2016). Growth Hormone Receptor in Melanoma: A Unique Approach to Therapy [Doctoral dissertation, Ohio University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1470923234

    APA Style (7th edition)

  • Basu, Reetobrata. Growth Hormone Receptor in Melanoma: A Unique Approach to Therapy. 2016. Ohio University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1470923234.

    MLA Style (8th edition)

  • Basu, Reetobrata. "Growth Hormone Receptor in Melanoma: A Unique Approach to Therapy." Doctoral dissertation, Ohio University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1470923234

    Chicago Manual of Style (17th edition)

ohiou1470923234
355
© 2016, all rights reserved.
This open access ETD is published by Ohio University and OhioLINK.