REGULATION OF PHENOTYPIC EXPRESSION AND PROLIFERATION OF S91 MELANOMA CELLS BY POTENT HORMONE ANALOGUES.

Persistent Link:
http://hdl.handle.net/10150/187849
Title:
REGULATION OF PHENOTYPIC EXPRESSION AND PROLIFERATION OF S91 MELANOMA CELLS BY POTENT HORMONE ANALOGUES.
Author:
ABDEL MALEK, ZALFA AMMAR.
Issue Date:
1984
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Cloudman S91 melanoma cells respond to a variety of endocrine factors, including melanotropins and steroid hormones. The murine S91 melanoma cell line, CCL 53.1, responded to α-melanocyte-stimulating hormone (α-MSH) in a dose- and a time-dependent manner, by increased tyrosinase activity. The minimal effective dose of α-MSH required to stimulate tyrosinase activity was 10⁻⁹M. By prolonging the exposure period of the cells to the hormone from 24 to 48, to 72 hours, the magnitude of tyrosinase stimulation was increased, but the minimal effective dose was not changed. α-MSH action involved elevation of intracellular cyclic AMP levels, and did not require the influx of extracellular calcium. Three melanotropin analogues, [Nle⁴, D-Phe⁷]-α-MSH, Ac-[Nle⁴, D-Phe⁷]-α-MSH₄₋₁₁-NH₂, and Ac-[Nle⁴, D-Phe⁷]- α-MSH₄₋₁₀-NH₂, have been shown to be more active than (alpha)-MSH in dispersing melanosomes within amphibian and reptilian integumental melanophores. These analogues also demonstrate prolonged activities and resistance to enzymatic degradation. The unique properties of these melanotropin analogues led to investigate their effects on the phenotypic expression and on the proliferation of S91 melanoma cells. The relative potency and the possible prolonged actions of the three [Nle⁴, D-Phe⁷] -substituted analogues were investigated and compared to those of α-MSH. The melanotropin analogues proved to be 100-1000 fold more active than α-MSH in stimulating tyrosinase activity. These analogues elicited significant tyrosinase activation following brief contact times with the cells, and maintained their stimulatory effects for days after removal from the culture flasks, and after the α-MSH effect had totally dissipated. Contrary to previous reports that melanotropins inhibit the proliferation of melanoma cells, α-MSH and [Nle⁴, D-Phe⁷] -α-MSH stimulated, rather than inhibited, the proliferation of CCL cells under culture conditions that allowed optimal phenotypic expression. Also, the effects of the steroids, β-estradiol, progesterone, and dexamethasone, on CCL cells were studied. Dexamethasone had the most remarkable effects, which involved stimulation of tyrosinase activity and inhibition of proliferation in monolayer culture and in soft agar. Furthermore, this study defined some of the factors that influence the endocrine responsiveness of melanoma cells. The results of this study have important implications for the regulation of phenotypic expression and of proliferation in S91 melanoma cells, and for the properties of the melanoma melanotropin receptor.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Cellular control mechanisms.; Cell physiology.; MSH (Hormone)
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Ecology and Evolutionary Biology; Graduate College
Degree Grantor:
University of Arizona
Advisor:
Meyskens, Frank

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleREGULATION OF PHENOTYPIC EXPRESSION AND PROLIFERATION OF S91 MELANOMA CELLS BY POTENT HORMONE ANALOGUES.en_US
dc.creatorABDEL MALEK, ZALFA AMMAR.en_US
dc.contributor.authorABDEL MALEK, ZALFA AMMAR.en_US
dc.date.issued1984en_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractCloudman S91 melanoma cells respond to a variety of endocrine factors, including melanotropins and steroid hormones. The murine S91 melanoma cell line, CCL 53.1, responded to α-melanocyte-stimulating hormone (α-MSH) in a dose- and a time-dependent manner, by increased tyrosinase activity. The minimal effective dose of α-MSH required to stimulate tyrosinase activity was 10⁻⁹M. By prolonging the exposure period of the cells to the hormone from 24 to 48, to 72 hours, the magnitude of tyrosinase stimulation was increased, but the minimal effective dose was not changed. α-MSH action involved elevation of intracellular cyclic AMP levels, and did not require the influx of extracellular calcium. Three melanotropin analogues, [Nle⁴, D-Phe⁷]-α-MSH, Ac-[Nle⁴, D-Phe⁷]-α-MSH₄₋₁₁-NH₂, and Ac-[Nle⁴, D-Phe⁷]- α-MSH₄₋₁₀-NH₂, have been shown to be more active than (alpha)-MSH in dispersing melanosomes within amphibian and reptilian integumental melanophores. These analogues also demonstrate prolonged activities and resistance to enzymatic degradation. The unique properties of these melanotropin analogues led to investigate their effects on the phenotypic expression and on the proliferation of S91 melanoma cells. The relative potency and the possible prolonged actions of the three [Nle⁴, D-Phe⁷] -substituted analogues were investigated and compared to those of α-MSH. The melanotropin analogues proved to be 100-1000 fold more active than α-MSH in stimulating tyrosinase activity. These analogues elicited significant tyrosinase activation following brief contact times with the cells, and maintained their stimulatory effects for days after removal from the culture flasks, and after the α-MSH effect had totally dissipated. Contrary to previous reports that melanotropins inhibit the proliferation of melanoma cells, α-MSH and [Nle⁴, D-Phe⁷] -α-MSH stimulated, rather than inhibited, the proliferation of CCL cells under culture conditions that allowed optimal phenotypic expression. Also, the effects of the steroids, β-estradiol, progesterone, and dexamethasone, on CCL cells were studied. Dexamethasone had the most remarkable effects, which involved stimulation of tyrosinase activity and inhibition of proliferation in monolayer culture and in soft agar. Furthermore, this study defined some of the factors that influence the endocrine responsiveness of melanoma cells. The results of this study have important implications for the regulation of phenotypic expression and of proliferation in S91 melanoma cells, and for the properties of the melanoma melanotropin receptor.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectCellular control mechanisms.en_US
dc.subjectCell physiology.en_US
dc.subjectMSH (Hormone)en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineEcology and Evolutionary Biologyen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMeyskens, Franken_US
dc.identifier.proquest8504744en_US
dc.identifier.oclc693373508en_US
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