Srikantan Vasantha, Valladares Michael, Rhim Johng S, Moul Judd W, Srivastava Shiv
Center for Prostate Disease Research, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20850-4799, USA.
Cancer Res. 2002 Dec 1;62(23):6812-6.
Expression of HEPSIN, a type II transmembrane serine protease in prostate cancer (CaP), has been highlighted by several studies analyzing CaP-specific gene expression alterations by cDNA microarray. Evaluations of the biological functions of HEPSIN in CaP cells are warranted for better assessment of its utility as a biomarker and/or therapeutic target. In stable clones of PC-3/HEPSIN transfectants, there was a dramatic reduction in the cell growth, cell invasion, and soft agar colony formation. A higher proportion of PC-3/HEPSIN cells were in the G(2)-M phase of the cell cycle, and there was also an increase in the cell population undergoing apoptosis. Preliminary analysis of HEPSIN transfections into LNCaP and DU145 cells further revealed cell growth-inhibitory effects. These results underscore that exogenous HEPSIN expression negatively regulates cell growth in metastatic CaP cell lines. Although the cause of the biological consequence of HEPSIN overexpression in primary CaP remains to be determined, the negative cell growth-regulatory effects of HEPSIN in metastatic CaP cells reported here have unraveled possible cellular and molecular mechanisms underlying observations that link decreased/loss of HEPSIN expression with poor prognosis of CaP.
通过cDNA微阵列分析前列腺癌（CaP）特异性基因表达变化的多项研究突出了II型跨膜丝氨酸蛋白酶HEPSIN在前列腺癌中的表达。为了更好地评估其作为生物标志物和/或治疗靶点的效用，有必要对HEPSIN在CaP细胞中的生物学功能进行评估。在PC-3/HEPSIN转染子的稳定克隆中，细胞生长、细胞侵袭和软琼脂集落形成显著减少。较高比例的PC-3/HEPSIN细胞处于细胞周期的G(2)-M期，且发生凋亡的细胞群体也有所增加。将HEPSIN转染到LNCaP和DU145细胞中的初步分析进一步揭示了细胞生长抑制作用。这些结果强调，外源性HEPSIN表达对转移性CaP细胞系中的细胞生长具有负调控作用。尽管原发性CaP中HEPSIN过表达的生物学后果的原因尚待确定，但此处报道的HEPSIN在转移性CaP细胞中的负性细胞生长调节作用揭示了将HEPSIN表达降低/缺失与CaP预后不良联系起来的观察结果背后可能的细胞和分子机制。
