Reduced Androgen Receptor Expression Accelerates the Onset of ERBB2 Induced Breast Tumors in Female Mice

Androgen receptor (AR) is commonly expressed in both the epithelium of normal mammary glands and in breast cancers. AR expression in breast cancers is independent of estrogen receptor alpha (ERα) status and is frequently associated with overexpression of the ERBB2 oncogene. AR signaling effects on breast cancer progression may depend on ERα and ERBB2 status. Up to 30% of human breast cancers are driven by overactive ERBB2 signaling and it is not clear whether AR expression affects any steps of tumor progression in this cohort of patients. To test this, we generated mammary specific Ar depleted mice (MARKO) by combining the floxed allele of Ar with the MMTV-cre transgene on an MMTV-NeuNT background and compared them to littermate MMTV-NeuNT, Arfl/+ control females. Heterozygous MARKO females displayed reduced levels of AR in mammary glands with mosaic AR expression in ductal epithelium. The loss of AR dramatically accelerated the onset of MMTV-NeuNT tumors in female MARKO mice. In this report we show that accelerated MMTV-NeuNT-dependent tumorigenesis is due specifically to the loss of AR, as hormonal levels, estrogen and progesterone receptors expression, and MMTV-NeuNT expression were similar between MARKO and control groups. MMTV-NeuNT induced tumors in both cohorts displayed distinct loss of AR in addition to ERα, PR, and the pioneer factor FOXA1. Erbb3 mRNA levels were significantly elevated in tumors in comparison to normal mammary glands. Thus the loss of AR in mouse mammary epithelium accelerates malignant transformation rather than the rate of tumorigenesis.

The use of visualization, onset-and-rime, story read-alouds, and discussion to improve diverse first graders' vocabulary and comprehension

It has long been known that vocabulary is essential in the development of reading. Because vocabulary leading to increased comprehension is important, it necessary to determine strategies for ensuring that the best methods of teaching vocabulary are used to help students make gains in vocabulary leading to reading comprehension. According to the National Reading Panel, multiple strategies that involve active engagement on the part of the student are more effective than the use of just one strategy. The purpose of this study was to determine if students' use of visualization, student-generated pictures of onset-and-rime-patterned vocabulary, and story read-alouds with discussion, would enable diverse first-grade students to increase their vocabulary and comprehension. In addition, this study examined the effect of the multimodal framework of strategies on English learners (ELs). This quasi-experimental study (N=69) was conducted in four first-grade classrooms in a low socio-economic school. Two treatment classes used a multimodal framework of strategies to learn weekly vocabulary words and comprehension. Two comparison classrooms used the traditional method of teaching weekly vocabulary and comprehension. Data sources included Florida Assessments for Instruction in Reading (FAIR), comprehension and vocabulary scores, and weekly MacMillan/McGraw Hill Treasures basal comprehension questions and onset-and-rime vocabulary questions. This research determined that the treatment had an effect in adjusted FAIR comprehension means by group, with the treatment group (adj M = 5.14) significantly higher than the comparison group ( adj M = -8.26) on post scores. However, the treatment means did not increase from pre to post, but the comparison means significantly decreased from pre to post as the materials became more challenging. For the FAIR vocabulary, there was a significant difference by group with the comparison adjusted post mean higher than the treatment's, although both groups significantly increased from pre to post. However, the FAIR vocabulary posttest was not part of the Treasures vocabulary, which was taught using the multimodal framework of strategies. The Treasures vocabulary scores were not significantly different by group on the assessment across the weeks, although the treatment means were higher than those of the comparison group. Continued research is needed in the area of vocabulary and comprehension instructional methods in order to determine strategies to increase diverse, urban students' performance.