| 1. |
- Massinen, Satu, et al.
(författare)
-
Functional interaction of DYX1C1 with estrogen receptors suggests involvement of hormonal pathways in dyslexia
- 2009
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 18:15, s. 2802-2812
-
Tidskriftsartikel (refereegranskat)abstract
- Dyslexia, or specific reading disability, is the unexpected failure in learning to read and write when intelligence and senses are normal. One of the susceptibility genes, DYX1C1, has been implicated in neuronal migration, but little is known about its interactions and functions. As DYX1C1 was suggested to interact with the U-box protein CHIP (carboxy terminus of Hsc70-interacting protein), which also participates in the degradation of estrogen receptors alpha (ERalpha) and beta (ERbeta), we hypothesized that the effects of DYX1C1 might be at least in part mediated through the regulation of ERs. ERs have shown to be important in brain development and cognitive functions. Indeed, we show that DYX1C1 interacts with both ERs in the presence of 17beta-estradiol, as determined by co-localization, co-immunoprecipitation and proximity ligation assays. Protein levels of endogenous ERalpha or exogenous ERbeta were reduced upon over-expression of DYX1C1, resulting in decreased transcriptional responses to 17beta-estradiol. Furthermore, we detected in vivo complexes of DYX1C1 with ERalpha or ERbeta at endogenous levels along neurites of primary rat hippocampal neurons. Taken together, our data suggest that DYX1C1 is involved in the regulation of ERalpha and ERbeta, and may thus affect the brain development and regulate cognitive functions. These findings provide novel insights into the function of DYX1C1 and link neuronal migration and developmental dyslexia to the estrogen-signaling effects in the brain.
|
|
| 2. |
- Yakimchuk, Konstantin, et al.
(författare)
-
Up-regulated estrogen receptor β2 in chronic lymphocytic leukemia
- 2012
-
Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 53:1, s. 139-144
-
Tidskriftsartikel (refereegranskat)abstract
- The estrogen receptors alpha (ERα) and beta (ERβ) have been demonstrated in mouse models to be important for immune system regulation, and are differentially expressed in lymphoid organs. One ERβ splice variant, ERβ2, inhibits the ERα-mediated estrogen effect, and expression might predict response to selective estrogen receptor modulators. We studied the expression of ERα, ERβ1 and ERβ2 in peripheral blood mononuclear cells from 26 patients with chronic lymphocytic leukemia (CLL) and 30 normal controls using immunocytochemistry. ERα expression was generally low, while ERβ1 was expressed in 65% of patients with CLL and in 83% of controls (NS). In contrast, nuclear staining for ERβ2 was positive in 69% of patients with CLL, but in only 17% of controls (p < 0.001). In CLL, ERβ2 was found in B- but not in T-lymphocytes. Our data show the expression of ERβ1 and ERβ2 in the majority of patients with CLL, suggesting that the ERs are important in CLL and might be used as therapeutic targets.
|
|
