@article {276,
	title = {Molecular profiling of prostatic acinar morphogenesis identifies PDCD4 and KLF6 as tissue architecture-specific prognostic markers in prostate cancer.},
	journal = {Am J Pathol},
	volume = {182},
	year = {2013},
	month = {2013 Feb},
	pages = {363-74},
	abstract = {<p>Histopathological classification of human prostate cancer (PCA) relies on the morphological assessment of tissue specimens but has limited prognostic value. To address this deficiency, we performed comparative transcriptome analysis of human prostatic acini generated in a three-dimensional basement membrane that recapitulates the differentiated morphological characteristics and gene expression profile of a human prostate glandular epithelial tissue. We then applied an acinar morphogenesis-specific gene profile to two independent cohorts of patients with PCA (total n = 79) and found that those with tumors expressing this profile, which we designated acini-like tumors, had a significantly lower risk of postoperative relapse compared with those tumors with a lower correlation (hazard ratio, 0.078; log-rank test P = 0.009). Multivariate analyses showed superior prognostic prediction performance using this classification system compared with clinical criteria and Gleason scores. We prioritized the genes in this profile and identified programmed cell death protein 4 (PDCD4) and Kruppel-like factor 6 (KLF6) as critical regulators and surrogate markers of prostatic tissue architectures, which form a gene signature that robustly predicts clinical prognosis with a remarkable accuracy in several large series of PCA tumors (total n = 161; concordance index, 0.913 to 0.951). Thus, by exploiting the genomic program associated with prostate glandular differentiation, we identified acini-like PCA and related molecular markers that significantly enhance prognostic prediction of human PCA.</p>
},
	keywords = {Acinar Cells, Aged, Apoptosis Regulatory Proteins, Cell Differentiation, Epithelial Cells, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Kruppel-Like Transcription Factors, Male, Middle Aged, Morphogenesis, Organ Specificity, Prognosis, Prostate, Prostatic Neoplasms, Proto-Oncogene Proteins, Recurrence, RNA-Binding Proteins, Tumor Markers, Biological},
	issn = {1525-2191},
	doi = {10.1016/j.ajpath.2012.10.024},
	author = {Li, Chi-Rong and Su, Jimmy J-M and Wang, Wei-Yu and Lee, Michael T-L and Wang, Ting-Yun and Jiang, Kuan-Ying and Li, Chein-Feng and Hsu, Jong-Ming and Chen, Chi-Kuan and Chen, Marcelo and Jiang, Shih-Sheng and Weaver, Valerie M and Tsai, Kelvin K-C}
}
@article {351,
	title = {HOXA9 regulates BRCA1 expression to modulate human breast tumor phenotype.},
	journal = {J Clin Invest},
	volume = {120},
	year = {2010},
	month = {2010 May},
	pages = {1535-50},
	abstract = {<p>Breast cancer 1, early onset (BRCA1) expression is often reduced in sporadic breast tumors, even in the absence of BRCA1 genetic modifications, but the molecular basis for this is unknown. In this study, we identified homeobox A9 (HOXA9) as a gene frequently downregulated in human breast cancers and tumor cell lines and noted that reduced HOXA9 transcript levels associated with tumor aggression, metastasis, and patient mortality. Experiments revealed that loss of HOXA9 promoted mammary epithelial cell growth and survival and perturbed tissue morphogenesis. Restoring HOXA9 expression repressed growth and survival and inhibited the malignant phenotype of breast cancer cells in culture and in a xenograft mouse model. Molecular studies showed that HOXA9 restricted breast tumor behavior by directly modulating the expression of BRCA1. Indeed, ectopic expression of wild-type BRCA1 phenocopied the tumor suppressor function of HOXA9, and reducing BRCA1 levels or function inhibited the antitumor activity of HOXA9. Consistently, HOXA9 expression correlated with BRCA1 in clinical specimens and with tumor aggression in patients lacking estrogen receptor/progesterone receptor expression in their breast tissue. These findings indicate that HOXA9 restricts breast tumor aggression by modulating expression of the tumor suppressor gene BRCA1, which we believe provides an explanation for the loss of BRCA1 expression in sporadic breast tumors in the absence of BRCA1 genetic modifications.</p>
},
	keywords = {Adult, Animals, BRCA1 Protein, Breast Neoplasms, Female, Gene Expression Regulation, Neoplastic, Homeodomain Proteins, Humans, Mice, Middle Aged, Models, Genetic, Neoplasm Transplantation, Phenotype, Receptors, Estrogen, Receptors, Progesterone, Treatment Outcome},
	issn = {1558-8238},
	doi = {10.1172/JCI39534},
	author = {Gilbert, Penney M and Mouw, Janna K and Unger, Meredith A and Lakins, Johnathon N and Gbegnon, Mawuse K and Clemmer, Virginia B and Benezra, Miriam and Licht, Jonathan D and Boudreau, Nancy J and Tsai, Kelvin K C and Welm, Alana L and Feldman, Michael D and Weber, Barbara L and Weaver, Valerie M}
}
