Myosin heavy chain gene expression in normal and hyperplastic human prostate tissue

BACKGROUND. Benign prostatic hyperplasia (BPH) is common among aging men. O ver 80% of males 50-60 years and older have various degrees of bladder outl et obstruction secondary to BPH. Despite the tremendous medical impact of B PH, its molecular pathophysiology remains unclear. Current BPH research foc uses on steroid hormonal effects, stromal-epithelial cell interaction, and oncogenes and growth factors. But little is known about the potential prost atic smooth muscle (SM) alterations that may occur during stromal hyperplas ia. METHODS. To study SM phenotypic modulation in hyperplastic prostatic growth , we isolated and characterized the 3' end of human SM myosin heavy chain ( SMMHC) cDNA as a molecular probe. Expression of SMMHC and nonmuscle myosin heavy chain (NMMHC) in human prostates was analyzed using Western blot, Nor thern blot, and in situ hybridization to determine if BPH tissue expresses significantly less SMMHC and more NMMHC than a normal prostate. In addition , a competitive, reverse transcription (RT) polymerase chain reaction (PCR) method was adapted to quantify SMMHC and NMMHC mRNA expression at the sens itivity level of 10(-21) mole per mg of wet tissue. RESULTS. Western blot, Northern blot, and in situ hybridization results rev eal that both SMMHC and NMMHC are expressed in the human prostate, while SM MHC is the predominant form found in normal prostate stroma. Results from c ompetitive RT-PCR analysis indicate that NMMHC mRNA expression is approxima tely 10(-20) mole/mg of tissue. The SMMHC mRNA expressed is approximately 1 0(-18) mole/mg-. No significant difference was found when NMMHC mRNA expres sion was compared between normal and BPH periurethral tissues. However, SMM HC expression was reduced almost fivefold in BPH compared to normal prostat e, despite an increase in prostatic stromal mass. CONCLUSIONS. Our results suggest the pathogenesis of BPH is associated with a unique type of SM proliferation. Such proliferation is characterized by downregulation of SMMHC mRNA expression but without upregulation of NMMHC m RNA expression, the pattern seen in proliferating SM cells in culture and i n other pathologic forms of SM hyperplasia (e.g., atherosclerosis). These f indings support a model of BPH typified by active smooth muscle proliferati on early in the disease process, and supports clinical observations that su ggest ongoing prostate growth of the prostate is minimal in older men. Ther apeutic strategies to prevent disease progression should therefore focus on early phases of prostatic growth. (C) 2000 Wiley-Liss, Inc.