the Sesame Workshop, the MacArthur Foundation, and the Lego Foundation. The sponsors of work by the authors on this manuscript had no role in (1) study design; (2) the collection, analysis, and interpretation of data; (3) the writing of the report; or (4) the decision to submit the paper for publication. The authors declare no conflicts of interest.

Growth of normal and neoplastic prostate is mediated by the androgen receptor (AR), a ligand-dependent transcription factor activated by high affinity androgen binding. The AR is highly expressed in recurrent prostate cancer cells that proliferate despite reduced circulating androgen. In this report, we show that epidermal growth factor (EGF) increases androgen-dependent AR transactivation in the recurrent prostate cancer cell line CWR-R1 through a mechanism that involves a posttranscriptional increase in the p160 coactivator transcriptional intermediary factor 2/glucocorticoid receptor interacting protein 1 (TIF2/GRIP1). Site-specific mutagenesis and selective MAPK inhibitors linked the EGF-induced increase in AR transactivation to phosphorylation of TIF2/GRIP1. EGF signaling increased the coimmunoprecipitation of TIF2 and AR. AR transactivation and its stimulation by EGF were reduced by small interfering RNA inhibition of TIF2/GRIP1 expression. The data indicate that EGF signaling through MAPK increases TIF2/GRIP1 coactivation of AR transactivation in recurrent prostate cancer.

The Interpersonal Support Evaluation List-12 (ISEL-12; Cohen, Mermelstein, Kamarck, & Hoberman, 1985) is broadly employed as a short-form measure of the traditional ISEL, which measures functional (i.e., perceived) social support. The ISEL-12 can be scored by summing the items to create an overall social support score; three subscale scores representing appraisal, belonging, and tangible social support have also been proposed. Despite extensive use, studies of the psychometric properties of ISEL-12 scores have been limited, particularly among Hispanics/Latinos, the largest and fastest growing ethnic group in the United States. The present study investigated the reliability, and structural and convergent validity of ISEL-12 scores using data from 5,313 Hispanics/Latinos who participated in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary study. Participants completed measures in English or Spanish, and identified their ancestry as Dominican, Central American, Cuban, Mexican, Puerto Rican, or South American. Cronbach’s alphas suggested adequate internal consistency for the total score for all languages and ancestry groups; coefficients for the subscale scores were not acceptable. Confirmatory factor analyses revealed that the one-factor and three-factor models fit the data equally well. Results from multigroup confirmatory factor analyses supported a similar one-factor structure with equivalent response patterns and variances between language groups and ancestry groups. Convergent validity analyses suggested that the total social support score related to scores of social network integration, life engagement, perceived stress, and negative affect (depression, anxiety) in the expected directions. The total score of the ISEL-12 can be recommended for use among Hispanics/Latinos.

Purpose: The androgen receptor (AR) is a liganddependent transcription factor that mediates gene expression and growth of normal and malignant prostate cells. In prostate tumors that recur after androgen withdrawal, the AR is highly expressed and transcriptionally active in the absence of testicular androgens. In these ''androgenindependent'' tumors, alternative means of AR activation have been invoked, including regulation by growth factors and their receptors in prostate cancer recurrence.Experimental Design and Results: In this report, we show that HER receptor tyrosine kinases 1 through 4 are expressed in the CWR-R1 recurrent prostate cancer cell line; their stimulation by epidermal growth factor (EGF) and heregulin activates downstream signaling, including mitogen-activated protein kinase and phosphatidylinositol-3 kinase and Akt pathways. We show that heregulin activates HER2 and HER3 and increases androgen-dependent AR transactivation of reporter genes in CWR-R1 cells. Tyrosine phosphorylation of HER2 and HER3, AR transactivation, and cell proliferation induced by heregulin were more potently inhibited by the EGFR/HER2 dual tyrosine kinase inhibitor GW572016 (lapatinib) than the EGFR-specific inhibitor ZD1839 (gefitinib). Basal proliferation in the absence of growth factors was also inhibited by GW572016 to a greater extent than ZD1839, suggesting that low level HER2/HER3 activation, perhaps by an autocrine pathway contributes to the proliferation signal.Conclusions: These data indicate that heregulin signaling through HER2 and HER3 increases AR transactivation and alters growth in a recurrent prostate cancer cell line. Therefore, inhibition of low-level HER2 signaling may be a potential novel therapeutic strategy in prostate cancer.

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