Estrogen receptor subtype agonist activation in human cutaneous squamous cell carcinoma cells modulates expression of CD55 and cyclin D1

Jing Lan, Xing Hua Gao, Rashmi Kaul

Research output: Contribution to journalArticle

Abstract

Clinical studies indicate gender bias in cutaneous squamous cell carcinoma (cSCC) incidence with worse prognosis observed in males than in females, suggesting estrogen-mediated protection. In contrast, recent clinical population studies show risk of cSCC by use of oral contraceptives, thus raising controversy. However, animal studies indicate a protective role of estrogen and estrogen receptor (ER)s in cSCC. Currently we have a poor understanding of ERs that are expressed in human cSCC cells and their possible role in malignant transformation. The focus of current study was to determine ER subtype specific expression on cSCC A431 cells and investigate if ER agonist based activation modulates tumor markers CD55 and Cyclin D1 in the cells. ERα, ERβ and G protein-coupled receptor (GPR30) subtype expression at mRNA and protein level was determined in human cSCC A431 cells by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. The localization of ER subtypes was determined by confocal microscopy. ER subtype agonist based activation on A431 cells was performed to investigate their role in modulating mRNA and protein expression of tumor markers CD55 and Cyclin D1. A431 cells differentially expressed all three ER subtypesERα, ERβ and GPR30 with GPR30 expression being the highest. Confocal studies confirmed that all three ER subtypes were expressed in the cytoplasm and ERα and ERβ lacked nuclear expression. Agonist based activation of both ERα and GPR30 significantly upregulated Cyclin D1 and CD55 expression. Blocking of GPR30 led to significantly downregulation of both Cyclin D1 and CD55 expression. In contrast to ERα and GPR30, ERβ activation significantly downregulated CD55 expression. Taken together, here we demonstrate for the first time that all three ERsERα, ERβ and GPR30 are expressed in human A431 cSCC cells and further ER agonist based activation modulates the expression of tumor markers CD55 and Cyclin D1.

Original languageEnglish
Pages (from-to)606-618
Number of pages13
JournalEXCLI Journal
Volume18
DOIs
StatePublished - 1 Jan 2019

Fingerprint

Cyclin D1
squamous cell carcinoma
cyclins
Estrogen Receptors
agonists
Squamous Cell Carcinoma
Estrogens
Skin
cells
Tumor Biomarkers
estrogen receptors
Down-Regulation
neoplasms
estrogens
Sexism
Messenger RNA
Oral Contraceptives
G-Protein-Coupled Receptors
oral contraceptives
Confocal Microscopy

Keywords

  • CD55
  • Cutaneous squamous cell carcinoma
  • Cyclin D1
  • Estrogen
  • Estrogen receptor
  • GPR30

Cite this

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title = "Estrogen receptor subtype agonist activation in human cutaneous squamous cell carcinoma cells modulates expression of CD55 and cyclin D1",
abstract = "Clinical studies indicate gender bias in cutaneous squamous cell carcinoma (cSCC) incidence with worse prognosis observed in males than in females, suggesting estrogen-mediated protection. In contrast, recent clinical population studies show risk of cSCC by use of oral contraceptives, thus raising controversy. However, animal studies indicate a protective role of estrogen and estrogen receptor (ER)s in cSCC. Currently we have a poor understanding of ERs that are expressed in human cSCC cells and their possible role in malignant transformation. The focus of current study was to determine ER subtype specific expression on cSCC A431 cells and investigate if ER agonist based activation modulates tumor markers CD55 and Cyclin D1 in the cells. ERα, ERβ and G protein-coupled receptor (GPR30) subtype expression at mRNA and protein level was determined in human cSCC A431 cells by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. The localization of ER subtypes was determined by confocal microscopy. ER subtype agonist based activation on A431 cells was performed to investigate their role in modulating mRNA and protein expression of tumor markers CD55 and Cyclin D1. A431 cells differentially expressed all three ER subtypesERα, ERβ and GPR30 with GPR30 expression being the highest. Confocal studies confirmed that all three ER subtypes were expressed in the cytoplasm and ERα and ERβ lacked nuclear expression. Agonist based activation of both ERα and GPR30 significantly upregulated Cyclin D1 and CD55 expression. Blocking of GPR30 led to significantly downregulation of both Cyclin D1 and CD55 expression. In contrast to ERα and GPR30, ERβ activation significantly downregulated CD55 expression. Taken together, here we demonstrate for the first time that all three ERsERα, ERβ and GPR30 are expressed in human A431 cSCC cells and further ER agonist based activation modulates the expression of tumor markers CD55 and Cyclin D1.",
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Estrogen receptor subtype agonist activation in human cutaneous squamous cell carcinoma cells modulates expression of CD55 and cyclin D1. / Lan, Jing; Gao, Xing Hua; Kaul, Rashmi.

In: EXCLI Journal, Vol. 18, 01.01.2019, p. 606-618.

Research output: Contribution to journalArticle

TY - JOUR

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AU - Lan, Jing

AU - Gao, Xing Hua

AU - Kaul, Rashmi

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AB - Clinical studies indicate gender bias in cutaneous squamous cell carcinoma (cSCC) incidence with worse prognosis observed in males than in females, suggesting estrogen-mediated protection. In contrast, recent clinical population studies show risk of cSCC by use of oral contraceptives, thus raising controversy. However, animal studies indicate a protective role of estrogen and estrogen receptor (ER)s in cSCC. Currently we have a poor understanding of ERs that are expressed in human cSCC cells and their possible role in malignant transformation. The focus of current study was to determine ER subtype specific expression on cSCC A431 cells and investigate if ER agonist based activation modulates tumor markers CD55 and Cyclin D1 in the cells. ERα, ERβ and G protein-coupled receptor (GPR30) subtype expression at mRNA and protein level was determined in human cSCC A431 cells by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. The localization of ER subtypes was determined by confocal microscopy. ER subtype agonist based activation on A431 cells was performed to investigate their role in modulating mRNA and protein expression of tumor markers CD55 and Cyclin D1. A431 cells differentially expressed all three ER subtypesERα, ERβ and GPR30 with GPR30 expression being the highest. Confocal studies confirmed that all three ER subtypes were expressed in the cytoplasm and ERα and ERβ lacked nuclear expression. Agonist based activation of both ERα and GPR30 significantly upregulated Cyclin D1 and CD55 expression. Blocking of GPR30 led to significantly downregulation of both Cyclin D1 and CD55 expression. In contrast to ERα and GPR30, ERβ activation significantly downregulated CD55 expression. Taken together, here we demonstrate for the first time that all three ERsERα, ERβ and GPR30 are expressed in human A431 cSCC cells and further ER agonist based activation modulates the expression of tumor markers CD55 and Cyclin D1.

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