Increased expression of hypoxia inducible factor-1alpha in rat and human prostate cancer.

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates genes involved in adaptation to hypoxia. Expression of HIF-1alpha was evaluated in rat and human prostate cancer cell lines. Increased expression of HIF-1alpha mRNA in rat prostate cancer cell lines and hypoxia-induced expression of HIF-1alpha protein in human prostate cancer cell lines are associated with increased cell growth rates and metastatic potential. HIF-1alpha mRNA was undetectable in the normal rat ventral prostate by Northern blot hybridization. HIF-1alpha protein expression and HIF-1 DNA binding activity were detected in normoxic PC-3 cells. Human prostate cancer cells plated at low density manifested higher functional HIF-1alpha expression than cells plated at high density independent of O2 tension. HIF-1alpha may become dysregulated in prostate cancer and thus drive the transcription of hypoxia-adaptive genes involved in tumor progression. This is also the first evidence that human cancer cells can express functional HIF-1alpha protein under normoxic conditions.

Differences in cultured cardiac fibroblast populations isolated from SHR and WKY rats.

1. The mechanisms whereby angiotensin converting enzyme inhibitors reverse cardiac remodelling appear to involve angiotensin and/or bradykinin receptors. Previously we reported that cultured rat cardiac fibroblasts express angiotensin II (AII) receptors. In the present study we compared AII receptor binding, gene expression of angiotensinogen and the AII, Subtype 1A (AT1A) receptor, as well as morphological changes induced by selected hormonal treatments in cultured fibroblasts derived from SHRLJ or WKYLJ rats. 2. Fibroblasts were isolated from adult rat left ventricle by either collagenase B or collagenase P digestion. Collagenase B yielded cell preparations from SHRLJ which grew slower than cells from WKYLJ rats and expressed nearly two-fold fewer AII receptors (compared to WKYLJ) while collagenase P yielded SHRLJ cells with similar binding and growth properties to WKYLJ. A good correlation was observed between receptor binding and AII receptor, type 1A (AT1A) mRNA concentrations. In the presence of steroids collagenase B cells showed a higher tendency to transform towards a preadipocyte cell type, estimated by the formation of lipid containing vacuoles/cell, while collagenase P cells, mainly the SHRLJ type, start to differentiate toward a myofibroblast-like cell type in the presence of AII, as calculated by the expression of alpha-smooth muscle actin. 3. From the results obtained in this study it is evident that a subset of fibroblasts can be isolated from the SHRLJ heart using collagenase B or P which differ in growth rates, AII receptor binding, AT1A and angiotensinogen mRNA levels, morphology and steroid responsiveness when compared to fibroblasts isolated from cardiac WKYLJ tissue.