Spontaneous immortalization of human dermal microvascular endothelial cells.

Aim: To establish and characterize a spontaneously immortalized human dermal microvascular endothelial cell line, iHDME1.

Methods: We developed a spontaneous immortalization method. This approach is based on the application of optimized culture media and culture conditions without addition of any exogenous oncogenes or carcinogens.

Altered TGF-β signaling in a subpopulation of human stromal cells promotes prostatic carcinogenesis.

Carcinoma-associated fibroblasts (CAF) play a critical role in malignant progression. Loss of TGF-β receptor II (TGFβR2) in the prostate stroma is correlated with prostatic tumorigenesis. To determine the mechanisms by which stromal heterogeneity because of loss of TGFβR2 might contribute to cancer progression, we attenuated transforming growth factor beta (TGF-β) signaling in a subpopulation of immortalized human prostate fibroblasts in a model of tumor progression.

Functional remodeling of benign human prostatic tissues in vivo by spontaneously immortalized progenitor and intermediate cells.

Tissue remodeling or regeneration is believed to initiate from multipotent stem and progenitor cells. We report here the establishment of two spontaneously immortalized adult non-tumorigenic human prostate epithelial cell lines, NHPrE1 and BHPrE1. NHPrE1 (CD133(high)/CD44(high)/OCT4(high)/PTEN(high)) was characterized as a putative progenitor cell, and BHPrE1 (p63(high)/p53(high)/p21(WAF1)(high)/RB(high)) was characterized as a putative epithelial intermediate cell.

Unopposed c-MYC expression in benign prostatic epithelium causes a cancer phenotype.

Background: We have sought to develop a new in vivo model of prostate carcinogenesis using human prostatic epithelial cell cultures. Human prostate cancers frequently display DNA amplification in the 8q24 amplicon, which leads to an increase in the copy number of the c-MYC gene, a finding that suggests a role for c-MYC in human prostate carcinogenesis. In addition overexpression of c-MYC in transgenic mouse models results in prostatic carcinogenesis.