Naslov
Expression profiles of metallothionein-I/II and megalin/LRP-2 in uterine cervical squamous lesions

Autori
Jakovac, Hrvoje ; Stašić, Nikola ; Krašević, Maja ; Jonjić, Nives ; Radošević-Stašić, Biserka

Izvornik
Virchows Archiv (0945-6317) 1 (2020); 33084977, 12

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Akt1/protein kinaseB phosphorylation .Biomarkers .CINlesions, low-densitylipoprotein receptor–related protein-2 . Metallothionein-I/II . Tumour microenvironment

Sažetak
Metallothioneins (MTs) are phylogenetically old cysteine-rich proteins, which are implicated in a variety of physiological and pathological processes. Their growth- regulating, anti-apoptotic and anti- inflammatory functions have been attributed not only to intracellular free radical scavenging and to zinc and copper regulation but also to the ability of secreted MT to bind on surface lipoprotein receptor- megalin/LRP2, which enables the endocytosis of MT-I/II and a wide range of other functionally distinct ligands. In the present study, we analysed the expression pattern of both proteins in 55 cases of premalignant transformation of cervical squamous cells, i.e. in low- and high-grade squamous intraepithelial lesion (LSIL and HSIL). The data showed that in LSIL (cervical intraepithelial neoplasia CIN1 ; N = 25) MTs were present only in basal and parabasal cells and that megalin was only weakly expressed. In HSIL (CIN2 ; N = 15 and CIN 3/carcinoma in situ ; N = 15), however, overexpression and colocalization of MT with megalin were found in the entire hyperplastic epithelium. Moreover, megalin immunoreactivity appeared on the glandular epithelium and vascular endothelium, as well as on lymphatic cells in stroma. Besides, multiple megalin-positive cells expressed phosphorylated Akt1, implying that MT- and/or megalin-dependent prosurvival signal transduction pathways might contribute to the development of severe cervical dysplasia. The data emphasize the diagnostic power of combined MT/ megalin analysis in pre-cancer screening.

Izvorni jezik
Engleski

Znanstvena područja
Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

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