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

• Published in: The Prostate 2000-08, Vol.44 (3), p.193-203
• Main Authors: Lin, Victor K., Wang, Di, Lee, I-Ling, Vasquez, Dolores, Fagelson, James E., McConnell, John D.
• Format: Article
• Language: English
• Subjects: Adult; Base Sequence; Biological and medical sciences; Blotting, Northern; Blotting, Western; BPH; DNA - chemistry; DNA Primers - chemistry; Electrophoresis, Polyacrylamide Gel; Gene Expression Regulation, Neoplastic; Humans; Image Processing, Computer-Assisted; In Situ Hybridization; Investigative techniques, diagnostic techniques (general aspects); Male; Medical sciences; Middle Aged; Molecular Sequence Data; Muscle, Smooth - pathology; myosin heavy chain; Myosin Heavy Chains - analysis; Myosin Heavy Chains - genetics; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; proliferation; Prostate - metabolism; Prostate - pathology; Prostatic Hyperplasia - etiology; Prostatic Hyperplasia - genetics; Prostatic Hyperplasia - metabolism; Prostatic Hyperplasia - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA - chemistry; RNA - isolation & purification; RT-PCR; Sequence Analysis, DNA; smooth muscle; Transurethral Resection of Prostate; Urinary system
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/1097-0045(20000801)44:3<193::AID-PROS3>3.0.CO;2-A

BACKGROUND Benign prostatic hyperplasia (BPH) is common among aging men. Over 80% of males 50–60 years and older have various degrees of bladder outlet obstruction secondary to BPH. Despite the tremendous medical impact of BPH, its molecular pathophysiology remains unclear. Current BPH research focuses on steroid hormonal effects, stromal‐epithelial cell interaction, and oncogenes and growth factors. But little is known about the potential prostatic smooth muscle (SM) alterations that may occur during stromal hyperplasia. 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, Northern 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 sensitivity level of 10−21 mole per mg of wet tissue. RESULTS Western blot, Northern blot, and in situ hybridization results reveal that both SMMHC and NMMHC are expressed in the human prostate, while SMMHC is the predominant form found in normal prostate stroma. Results from competitive RT‐PCR analysis indicate that NMMHC mRNA expression is approximately 10−20 mole/mg of tissue. The SMMHC mRNA expressed is approximately 10−18 mole/mg. No significant difference was found when NMMHC mRNA expression was compared between normal and BPH periurethral tissues. However, SMMHC expression was reduced almost fivefold in BPH compared to normal prostate, 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 mRNA expression, the pattern seen in proliferating SM cells in culture and in other pathologic forms of SM hyperplasia (e.g., atherosclerosis). These findings support a model of BPH typified by active smooth muscle proliferation early in the disease process, and supports clinical observations that suggest ongoing prostate growth of the prostate is minimal in older men. Therapeutic strategies to prevent disease progression should therefore focus on earl