Merlin, the product of NF2 gene, is associated with aromatase expression and estrogen formation in human liver tissues and liver cancer cells

Cocciadiferro, Letizia; Miceli, Vitale; Granata, Orazia M.; Carruba, Giuseppe

doi:10.1016/j.jsbmb.2016.05.023

Cited by 14 publications

(24 citation statements)

References 31 publications

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“…Therefore, the elevated estrogen production induced to a higher aromatase activity could induce liver tumor cell growth through a variant ERα-mediated mechanism. Furthermore, the modification in activity of aromatase-estrogen-amphiregulin-EGF-R axis in issue injury or inflammation could result in growth of tumours such as liver, breast or prostate and progress of chronic diseases such as diabetes, obesity, Alzheimer's and heart disease [140]. Other studies also confirm that the change in ERα status (from wild type ERα66 to the ERα36 splice variant, but not to the ERα46 splice variant) influences HCC development [141].…”

Section: Activity Of Aromatase/estrogens/ers (And Variants) In Hccmentioning

confidence: 93%

“…Moreover, elevated expression of AREG corresponds with ubiquitous expression of hERalpha46 (human variant of ERα) [138,139] and occasional expression of the hERβ2/Cx (human variant of ERβ) [139]. Either none or a low expression of wild-type ERα and ERβ is observed in liver cancer cells and malignant tissues, and the pattern of wtERα is inversely related to aromatase expression [140]. Therefore, the elevated estrogen production induced to a higher aromatase activity could induce liver tumor cell growth through a variant ERα-mediated mechanism.…”

Section: Activity Of Aromatase/estrogens/ers (And Variants) In Hccmentioning

confidence: 99%

“…A study by Carruba et al [138,139] carried out on nontumoral, cirrhotic, and malignant human liver tissue samples (in vivo) and in HepG2, HuH7, and HA22T cells (in vitro) revealed for the first time that the level of the aromatase enzyme is significantly increased in liver cancer cells (malignant human liver tissue and HepG2 hepatoma cells), which leads to an increase in the local conversion of estrogens from androgens. Aromatase expression is moderate (or intermediate) in cirrhotic human liver samples (or HuH7 cells) and undetectable (or very low) in nontumoral human liver tissue (or HA22T cells) [138][139][140]. The level of local androgen aromatization is correlated with the degree of malignancy of the liver tissue/cell line.…”

Section: Activity Of Aromatase/estrogens/ers (And Variants) In Hccmentioning

confidence: 99%

“…The level of local androgen aromatization is correlated with the degree of malignancy of the liver tissue/cell line. Therefore, locally elevated estrogen formation affects the development and progression of cancer tissues and cells (HCC, HepG2) by activating the rapid signalling pathway mediated via amphiregulin (AREG; a member of the EGF family), a ligand of EGF-R (epidermal growth factor receptor) [138,140]. Moreover, elevated expression of AREG corresponds with ubiquitous expression of hERalpha46 (human variant of ERα) [138,139] and occasional expression of the hERβ2/Cx (human variant of ERβ) [139].…”

Section: Activity Of Aromatase/estrogens/ers (And Variants) In Hccmentioning

confidence: 99%

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Sex Hormone-Dependent Physiology and Diseases of Liver

Kur

Kolasa

Misiakiewicz-Has

et al. 2020

IJERPH

111

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Sexual dimorphism is associated not only with somatic and behavioral differences between men and women, but also with physiological differences reflected in organ metabolism. Genes regulated by sex hormones differ in expression in various tissues, which is especially important in the case of liver metabolism, with the liver being a target organ for sex hormones as its cells express estrogen receptors (ERs: ERα, also known as ESR1 or NR3A; ERβ; GPER (G protein-coupled ER, also known as GPR 30)) and the androgen receptor (AR) in both men and women. Differences in sex hormone levels and sex hormone-specific gene expression are mentioned as some of the main variations in causes of the incidence of hepatic diseases; for example, hepatocellular carcinoma (HCC) is more common in men, while women have an increased risk of autoimmune liver disease and show more acute liver failure symptoms in alcoholic liver disease. In non-alcoholic fatty liver disease (NAFLD), the distinction is less pronounced, but increased incidences are suggested among men and postmenopausal women, probably due to an increased tendency towards visceral fat accumulation.

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Section: Activity Of Aromatase/estrogens/ers (And Variants) In Hccmentioning

confidence: 93%

Section: Activity Of Aromatase/estrogens/ers (And Variants) In Hccmentioning

confidence: 99%

Section: Activity Of Aromatase/estrogens/ers (And Variants) In Hccmentioning

confidence: 99%

Section: Activity Of Aromatase/estrogens/ers (And Variants) In Hccmentioning

confidence: 99%

See 2 more Smart Citations

Sex Hormone-Dependent Physiology and Diseases of Liver

Kur

Kolasa

Misiakiewicz-Has

et al. 2020

IJERPH

111

View full text Add to dashboard Cite

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“…In EGFR- and HER2-overexpression transgenic models larger tumors appear that respond to tyrosine kinase inhibitors [ 68 ]. Although the relation among aromatase, estrogens, and EGFR have been studied in different tumors such as breast [ 69 ], endometrial [ 70 ], lung [ 71 ], and liver [ 72 ] tumors, among others, the relationship between EGFR and aromatase in pituitary gland or prolactinomas has not been well analyzed to date, but its participation should not be ruled out.…”

Section: Estrogens Prolactin and Aromatasementioning

confidence: 99%

Relation among Aromatase P450 and Tumoral Growth in Human Prolactinomas

Garcı́a-Barrado

Blanco

Iglesias-Osma

et al. 2017

IJMS

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The pituitary gland is part of hypothalamic-pituitary–gonadal axis, which controls development, reproduction, and aging in humans and animals. In addition, the pituitary gland is regulated mainly by hormones and neurotransmitters released from the hypothalamus and by systemic hormones secreted by target glands. Aromatase P450, the enzyme responsible for the catabolization of aromatizable androgens to estrogens, is expressed in different parts of body, including the pituitary gland. Moreover, aromatase P450 is involved in sexual dimorphism where alteration in the level of aromatase can initiate a number of diseases in both genders. On the other hand, the direct actions of estrogens, mainly estradiol, are well known for stimulating prolactin release. Numerous studies have shown that changes in the levels of estrogens, among other factors, have been implicated in the genesis and development of prolactinoma. The pituitary gland can produce estradiol locally in several types of endocrine cells, and it is possible that aromatase could be responsible for the maintenance of the population of lactotroph cells and the modulation of the action of central or peripheral regulators. Aromatase overexpression due to inappropriate gene regulation has clinical effects such as the pathogenesis of prolactinomas. The present study reports on the synthesis of pituitary aromatase, its regulation by gonadal steroids, and the physiological roles of aromatase on pituitary endocrine cells. The involvement of aromatase in the pathogenesis of pituitary tumors, mainly prolactinomas, through the auto-paracrine production of estradiol is reviewed.

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