It is prevailingly thought that estrogen signaling is not involved in development of estrogen receptor (ER)-negative breast cancer. However, there is evidence indicating that ovariectomy prevents the development of both ER-positive and -negative breast cancer, suggesting that estrogen signaling is involved in the development of ER-negative breast cancer. Previously, our laboratory cloned a variant of ER-α, ER-α36, and found that ER-α36 mediated nongenomic estrogen signaling and is highly expressed in ER-negative breast cancer cells. In this study, we found that ER-α36 was highly expressed in 10/12 cases of triple-negative breast cancer. We investigated the role of mitogenic estrogen signaling mediated by ER-α36 in malignant growth of triple-negative breast cancer MDA-MB-231 and MDA-MB-436 cells that express high levels of ER-α36 and found that these cells strongly responded to mitogenic estrogen signaling both in vitro and in vivo. Knockdown of ER-α36 expression in these cells using the small hairpin RNA method diminished their responsiveness to estrogen. ER-α36 physically interacted with the EGFR/Src/Shc complex and mediated estrogen-induced phosphorylation of epidermal growth factor receptor (EGFR) and Src. EGFR signaling activated ER-α36 transcription through an AP1 site in the ER-α36 promoter, and ER-α36 expression was able to stabilize EGFR protein. Our results, thus demonstrated that ER-α36 mediates nongenomic estrogen signaling through the EGFR/Src/ERK signaling pathway in ER-negative breast cancer cells and suggested that a subset of ER-negative breast tumors that expresses ER-α36, retains responsiveness to mitogenic estrogen signaling.

Busa is an old endangered autochthonous breed of the western Balkan, especially Bosnia-Herzegovina, Kosovo and Albania. A related breed is Gatacko, derived from Busa × Tirolean Grey crossbreds. Fifteen purebred Busa cattle and thirteen Gatacko animals were genotyped for polymorphisms at the kappa-casein gene by a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) essay. The alleles A, B and C were found and the allelic frequencies were 0.46 (A), 0.46 (B) and 0.08 (C) in Busa cattle and 0.58 (A) and 0.42 (B) in Gatacko. Only AA, AB, BB and BC genotypes occurred. Further alleles were not detected and are therefore either absent in both populations or rare. The allele »B« found in this small population will be useful for a sire selection program in the future.

The main aim of this paper is to present epidemiological indicators of oral health among six-year olds in Bosnia and Herzegovina (BH) and to analyze values of dmft index and dental treatment needs in order to identify differences in parts of the country. Another aim is to identify the needs from the public oral health care system in Bosnia and Herzegovina related to early permanent dentition by analyzing the condition of first permanent molars (FPM) as an indicator of oral health of permanent dentition. Survey was carried out in 2004 in 8 cantons of the Federation of BH (FBH) and in the Republic of Srpska (RS). Final sample included 560 participants aged six (mean 6.2, SD +/- 0.87). One dental team clinically examined all participants according to WHO methodology and criteria. The parameters used were: dmft index, DMFT index of first permanent molars (FPM), presence of sealants and treatment needs. A questionnaire about oral health habits had been administered. Dmft was 6.71 in that the d-component constituted the major part of the index. DMFT index of FPM was 0.61 (SD +/- 1.08). Percentage of caries free participants aged 6 was 6.8%. Average number of FPM with fissure sealants in BH was 0.25 (SD +/- 0.78). Significant demographic differences in dmft index, DMFT FPM and treatment needs were identified. Most participants (48.5%) had their first dental visit between the ages of five and seven. National oral health goal for Bosnia and Herzegovina should be to develop and implement disease prevention programs based on education of both parents and dental practitioners. It is necessary to improve access to dental care and shift focus from curative to preventive procedures. It is also necessary to set real goals for improvement of oral health which can be achieved within a desired time frame, as well as to precisely define measures to be taken.