Naϩ /I Ϫ symporter (NIS)-mediated iodide uptake into thyroid follicular cells serves as the basis of radioiodine therapy for thyroid cancer. NIS protein is also expressed in the majority of breast tumors, raising potential for radionuclide therapy of breast cancer. KT5823, a staurosporine-related protein kinase inhibitor, has been shown to increase thyroid-stimulating hormone-induced NIS expression, and thus iodide uptake, in thyroid cells. In this study, we found that KT5823 does not increase but decreases iodide uptake within 0.5 h of treatment in trans-retinoic acid and hydrocortisone-treated MCF-7 breast cancer cells. Moreover, KT5823 accumulates hypoglycosylated NIS, and this effect is much more evident in breast cancer cells than thyroid cells. The hypoglycosylated NIS is core glycosylated, has not been processed through the Golgi apparatus, but is capable of trafficking to the cell surface. KT5823 impedes complex NIS glycosylation at a regulatory point similar to brefeldin A along the N-linked glycosylation pathway, rather than targeting a specific N-glycosylated site of NIS. KT5823-mediated effects on NIS activity and glycosylation are also observed in other breast cancer cells as well as human embryonic kidney cells expressing exogenous NIS. Taken together, KT5823 will serve as a valuable pharmacological reagent to uncover mechanisms underlying differential NIS regulation between thyroid and breast cancer cells at multiple levels. Endocrinology, published January 5, 2011, 10.1210/en.2010 This article appears in Androgen Receptor Expression in the Caput Epididymal Epithelium Is Essential for Development of the Initial Segment and Epididymal Spermatozoa TransitLaura O'Hara, Michelle Welsh, Philippa T. K. Saunders, and Lee B. SmithThe epididymis plays an essential role in male fertility, and disruption of epididymal function can lead to obstructive azoospermia. Formation and function of the epididymis is androgen-dependent. The androgen receptor (AR) is expressed in both the stromal and epithelial compartments of the epididymis, and androgen action mediated via stromal cells is vital for its normal development and function. However the impact of epithelial specific AR-dependent signaling in the epididymis remains underexplored. To address this, we used conditional gene-targeting in mice to selectively ablate AR from the caput epididymal epithelium, and characterized the resulting phenotype at multiple postnatal ages. Caput epithelium androgen receptor knock-out (CEARKO) mice have normal serum testosterone concentrations at day (d) 21 and d100, but do not develop an epididymal initial segment. The remaining caput epithelium displays a significant decrease in epithelial cell height from d11 and lumen diameter from d21 and disruption of the smooth muscle layer of the caput epididymis at d100. From d21, CEARKO mice accumulate cell debris, proteinaceous material, and, at later ages, spermatozoa in their efferent ducts, which prevents normal passage of spermatozoa from the testis into the cauda epididymis resu...
Recent instability in the global financial markets has highlighted the need for companies to remain vigilant in detecting fraud and other forms of misconduct. Encouraging whistleblowing by persons who have knowledge of corporate misconduct or fraud is important. Legislative provisions protecting whistleblowers and the integration of whistleblower programmes within a company's corporate governance framework are two strategies that may encourage whistleblowing. Legislative provisions protecting whistleblowers were introduced into the Australian Corporations Act 2001 (Cth) in 2004. In 2007 the revised Australian Stock Exchange Principles recommended that listed corporations establish a code of conduct, and suggested that the code imbed within it reference to the way in which whistleblower disclosures are handled. While there have been various studies investigating whistleblowing programmes in the public sector, prior to this study there was virtually no empirical research into corporate sector whistleblowing in Australia. This paper examines the findings of an empirical study into the use of the whistleblowing protection provisions contained in the Australian Corporations Act 2001 (Cth) and the adoption of whistleblowing programmes as recommended by the Australian Stock Exchange Principles by Australia's leading 200 listed companies.
This article is part of a larger international investigation of the effects of a country's legal origins on the style of business regulation. We employ an innovative 'leximetric' methodology to numerically code the protective strength of Australian corporate law for both shareholder and creditor protection for the period 1970 to 2010. This leximetric methodology has been used in a prominent international debate concerning the development of legal rules and the effects of different styles of regulation on a range of economic outcomes-the legal origins debate. Drawing on similar data compiled by Armour, Deakin, Lele and Siems in five other countries (France, Germany, India, the UK and the US) for the period 1970 to 2005, we compare changes in the level of protection afforded to Australian shareholders and creditors with developments in other countries. Our analysis finds that in Australia there was a sustained upward trend in shareholder protection, but not in the case of creditor protection. Compared to the five other countries, the level of protection afforded to shareholders under Australian law was relatively high, and this was the case for the level of protection afforded to creditors as well. We also examine the extent of convergence and divergence in shareholder and creditor protection among the countries in the study. We find persistent divergence in shareholder protection, with the extent of divergence in 2005 similar to that in 1970. For creditor protection, we find increasing divergence among the countries over the period of study. Our findings are not supportive of legal origins theory.
This article is a unique investigation of the interaction between sociocultural perceptions of women in Malaysia and reforms implemented in that jurisdiction to promote gender diversity on corporate boards. It adopts a law and social movements perspective to better understand the legal reforms that have emerged, often amid fraught interactions between the state and women's rights activists due to their conflicting conceptions of gender roles. The article draws on empirical data to shed light on the practical workings of the reforms, ascertaining the perspective of insiders through interviews and examining the composition of the boards of 30 of the largest listed companies. While an increase in the representation of women on corporate boards suggests that the reforms have facilitated progress towards gender equality, such progress must be viewed in the context of prevalent conservative perceptions of gender roles, and sustained state resistance against women's rights activists, which together impede progress towards substantive equality.
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