Estradiol promotes rapid degradation of HER3 in ER-positive breast cancer cell line MCF-7

HER3, a member of the receptor tyrosine kinase super family, is overexpressed in a number of cancers, and is associated with malignant phenotypes. Control of the protein stability of the membrane, as well as nuclear receptors, has been known to be an important process affecting tumor cells; however, their relationships have yet to be elucidated. In this study, we demonstrate that estradiol promotes rapid degradation of HER3 via the proteasome pathway in ER-positive breast cancer, MCF-7. ER prevented HER3 degradation, and knockdown of ER expression by si-RNA promoted rapid degradation of HER3. Breakdown of HER3 and ER were regulated by a ubiquitin ligase Nedd4-1 in the presence of estradiol stimulation. We speculate that estradiol quickly degrades ER, making HER3 accessible by Nedd4-1, and leads to the rapid degradation of HER3. In addition, knockdown of ubiquitin ligase Nedd4-1 enhances estradiol induced cell proliferation. These results indicate that HER3 and Nedd4-1 in ER-positive breast cancers might be an important therapeutic target. Keywords: HER3, Nedd4-1, Estradiol, ER, Degradatio

Walking munu and jumping bibi: sound symbolism in (non)words produced by Turkish speakers

Contrary to the classic idea of arbitrariness in mappings between words and meanings, many languages have words that mimic the sounds of their referents (onomatopoeia) and other subtler sound symbolic associations. However, our knowledge concerning the characteristics of sound-meaning links is still limited. Previous research mostly focused on languages with a large (e.g., Japanese) or limited (e.g., English) inventory of sound symbolic words. We conducted a word-production study with native speakers of Turkish, a language with a moderate amount of sound symbolic words, and examined links between sound properties (e.g., voiced vs. voiceless) and semantic dimensions (e.g., size, speed) in describing motions. Some of the sound-meaning links identified were the links found in Japanese and English samples in previous studies (Saji et al., 2019), whereas many seem to be specific to Turkish. This study provides initial evidence for language-specific sound symbolism in Turkish and links that are consistent across languages

Successful use of linezolid for refractory Mycobacterium abcessus infection: A case report

A 51-year-old male patient was receiving treatment for Mycobacterium abscessus infection for approximately 10 years. However, as his condition gradually progressed to type II respiratory insufficiency, he was referred to our hospital, which was near his home. Computed tomography on his first visit revealed an abscess in the right lower lobe. Because respiratory insufficiency was evident, he was admitted the same day. We began treatment with meropenem, amikacin, and clarithromycin, but his symptoms did not improve. In accordance with the 2007 American Thoracic Society/Infectious Diseases Society of America statement, we administered linezolid, which resulted in gradual improvement in his physical status and imaging findings. Keywords: Nontuberculous mycobacterium, Mycobacterium abscessus, Linezoli

From green to turquoise: exploring age and socioeconomic status in the acquisition of color terms

Previous research demonstrates that children delineate more nuanced color boundaries with increased exposure to their native language. As socioeconomic status (SES) is known to correlate with differences in the amount of language input children receive, this study attempts to extend previous research by asking how both age (age 3 vs 5) and SES (under-resourced vs advantaged) might impact color name acquisition of preschool children. The results confirm the findings of previous research, showing that older children labeled the color continuum more accurately than did younger participants. In addition, we found that while SES did not make a difference in how children labeled the continuum using basic color terms (e.g. blue), basic color terms with achromatic modifiers (e.g. light blue), and compound terms (e.g. blueish-green), 5-year-olds from more advantaged economic environments used significantly more non-basic color terms (e.g. turquoise) compared to their counterparts from under-resourced environments. We suggest that, as children hear more non-basic terms, these world-to-word mappings become solidified, and exposure to such labels may contribute to the timing of when children can map those terms to the color continuum

Oestrogen receptor-β1 but not oestrogen receptor-βcx is of prognostic value in apocrine carcinoma of the breast

Apocrine carcinoma of the breast, which frequently expresses oestrogen receptor-β (ER-β) in the absence of ER-α and only infrequently is treated endocrinologically, gives an opportunity to investigate the clinicopathological role of ER-β in breast cancer independent of ER-α expression or tamoxifen treatment. Several isotypes of ER-β, ER-β1-5 etc., have been identified thus far; however, the clinicopathological importance of each ER-β isotype in breast cancer is still uncertain. Here we aimed to clarify the clinicopathological importance of ER-β1 and ER-βcx (ER-β2) in apocrine carcinomas, immunohistochemically examining expressions of ER-β1 and ER-βcx in 47 apocrine carcinomas. Positivity for ER-β1 and ER-βcx was observed in 41 (87%) and 18 (38%) of 47 cases, respectively. ER-β1 positivity was related to smaller tumor size (P=0.0359), lower histological grade (P=0.0322), and higher disease-free survival (P\u3c0.0001), whereas ER-βcx status was related to none of these parameters. ER-β1 positivity was also associated with favorable clinical outcome in 24 so-called triple-negative (ER-α-negative/PR-negative/HER2- negative) apocrine carcinomas. ER-β1 itself, independent of ER-α expression and tamoxifen treatment, seems to have a tumor-suppressive effect, at least in apocrine carcinomas. Further study of ER-β1 is desired to optimize breast cancer treatment. © The Authors 2008

E3 Ubiquitin Ligase NEDD4 Affects Estrogen Receptor α Expression and the Prognosis of Patients with Hormone Receptor-Positive Breast Cancer

Neural precursor cell-expressed developmentally downregulated 4–1 (NEDD4) is an E3 ligase that leads to the degradation of proteins, including estrogen receptor α. We evaluated whether the expression level of NEDD4 affected the outcome of breast cancer patients. We performed a retrospective cohort study enrolling 143 patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer. Of the 66 patients with high NEDD4 mRNA levels (high NEDD4 group) and 77 patients with low NEDD4 mRNA levels (low NEDD4 group), 98.4% and 96.1%, respectively, of the patients had received neoadjuvant/adjuvant hormone therapy. Disease-free survival and overall survival were significantly longer in the low NEDD4 group than in the high NEDD4 group (p = 0.048 and p = 0.022, respectively). Western blotting revealed a high expression of estrogen receptor α in the NEDD4-knockdown culture cells. The proliferation of NEDD4-knockdown cells treated with tamoxifen or estradiol deprivation was suppressed, compared with that of NEDD4-expressing cells. Knockdown of NEDD4 in breast cancer cells induced the accumulation of estrogen receptor α and increased sensitivity to hormone therapy. In summary, this mechanism may lead to a better prognosis in hormone receptor-positive breast cancer patients with a low expression of NEDD4