O-Glycosylation of human sex hormone-binding globulin is essential for inhibition of estradiol-induced MCF-7 breast cancer cell proliferation

 O-Glycosylation of human sex hormone-binding globulin is essential for inhibition of estradiol-induced MCF-7 breast cancer cell proliferation},
  author={Mariangela Raineri and Maria Graziella Catalano and Geoffrey L. Hammond and George V. Avvakumov and Roberto Frairia and Nicoletta Fortunati},
  journal={Molecular and Cellular Endocrinology},
Sex hormone-binding globulin (SHBG) and estradiol cross-talk in breast cancer cells.
  • N. Fortunati, M. Catalano
  • Biology, Medicine
    Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
  • 2006
It is suggested that SHBG is one of the regulators of growth and apoptosis of estrogen-dependent breast cancer cells, with the ultimate result of inhibiting estradiol-mediated cell growth and antiapoptosis.
Micro‐ and macroheterogeneity of N‐glycosylation yields size and charge isoforms of human sex hormone binding globulin circulating in serum
This work represents the most detailed structural map of the heterogeneous hSHBG glycosylation, which is a prerequisite for investigating the functional aspects of the hSH BG glycans.
Sex hormone-binding globulin selectively modulates estradiol-regulated genes in MCF-7 cells.
It is demonstrated that in breast cancer cells, sex hormone-binding globulin is effective on few selected genes which are involved in cell growth and apoptosis or related to cell estrogen-dependence and that the protein regulation of estradiol effect is selected and specific.
Quantitative Analysis of Sex-Hormone-Binding Globulin Glycosylation in Liver Diseases by Liquid Chromatography-Mass Spectrometry Parallel Reaction Monitoring.
In general, a significant contribution of different liver disease etiologies to the observed changes in glycosylation is not found; however, elevation of the newly reported HexNAc(4)Hex(6) N-glycoform is associated with alcoholic liver disease.
Sex Hormone-Binding Globulin (SHBG), estradiol and breast cancer
Glycosylation may influence sex hormone-binding globulin measurements.
Molecular mechanisms of the D327N SHBG protective role on breast cancer development after estrogen exposure
Evidence is provided for the mechanism of D327N SHBG protective action in counteracting estradiol action and a significantly higher frequency of Asp327Asn polymorphism in women not developing breast cancer after estrogen exposure.
Colocalization of Androgen Binding Protein, Oxytocin Receptor, Caveolin 1 and Proliferation Marker p21 in Benign Prostate Hyperplasia
Observations indicate an interaction of ABP and OTR, associated with caveolin 1, which may account in part for known non‐genomic actions of gonadal steroids in benign prostate hyperplasia.


Selective removal of glycosylation sites from sex hormone-binding globulin by site-directed mutagenesis.
Site-directed mutagenesis of a human SHBG cDNA has enabled us to selectively disrupt the known glycosylation sites individually and in various combinations, and it was found that the presence of carbohydrates is not an absolute requirement for the secretion of SHBG from these cells, but the absence of both N-linked oligosaccharides reduced the amount of SH BG in the culture medium.
The additionally glycosylated variant of human sex hormone‐binding globulin (SHBG) is linked to estrogen‐dependence of breast cancer
The frequency of the SHBG variant was significantly higher in ER+/PR+ tumors and in tumors diagnosed in patients over 50 years of age than in the control group, suggesting the existence of a close link between the estrogen‐dependence of breast cancer and the additionally glycosylated SHBG, further supporting a critical role of the protein in the neoplasm.
Sex steroid binding protein exerts a negative control on estradiol action in MCF-7 cells (human breast cancer) through cyclic adenosine 3',5'-monophosphate and protein kinase A.
The present study strongly confirms the previous observation that SBP inhibits the estradiol induction of MCF-7 cell growth, appropriately suggesting that this SBP action, a consequence of the interaction with the receptor, is likely to be mediated by cAMP and PKA.
Binding of an extracellular steroid-binding globulin to membranes and soluble receptors from human breast cancer cells (MCF-7 cells).
Specific binding of SHBG to receptor on membranes isolated from MCF-7 cells demonstrated that sex hormone-binding globulin (SHBG) binds to a single class of sites on membranes.
Biologically active steroids activate receptor-bound human sex hormone-binding globulin to cause LNCaP cells to accumulate adenosine 3',5'-monophosphate.
The binding of human sex hormone-binding globulin to a human prostatic cancer cell line (LNCaP) and the results of that binding were examined and demonstrate an additional mode of action of steroid hormones, one that does not require that the steroid interact with a steroid receptor.
Human variant sex hormone-binding globulin (SHBG) with an additional carbohydrate chain has a reduced clearance rate in rabbit.
It is demonstrated that an additional carbohydrate chain on hSHBG decreases the clearance rate of this protein, and further study will be required to determine whether it is associated with higher serum SHBG concentration.
Molecular analyses of a human sex hormone-binding globulin variant: evidence for an additional carbohydrate chain.
Genomic DNA was isolated from an individual who is homozygous for a sex hormone-binding globulin (SHBG) variant that resolves into three molecular weight forms of 56K, 52K, and 48K during electrophoresis under denaturing conditions and sequence analysis revealed a point mutation encoding an amino acid substitution at residue 327 in the SHBG polypeptide.
Human sex hormone-binding globulin gene expression in transgenic mice.
The sex hormone-binding globulin gene (shbg) is expressed in the liver and testis as well as in several other tissues that play important roles in reproduction and the consequences of overexpressing this gene in vivo are studied.