Expression of c-kit and kit-ligand in benign and malignant prostatic tissues.
Expression of c-kit and kit-ligand in benign and malignant prostatic tissues.
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DOI：
10.14670/hh-15.365
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发表时间：
2000-04
影响因子：
2
通讯作者：
Reiner Simak;P. Capodieci;David W. Cohen;W. R. Fair;Howard I. Scher;Jonathan Melamed;M. Drobnjak;Warren D. W. Heston;U. Stix;G. Steiner;Carlos Cordon-Cardo
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作者：
Reiner Simak;P. Capodieci;David W. Cohen;W. R. Fair;Howard I. Scher;Jonathan Melamed;M. Drobnjak;Warren D. W. Heston;U. Stix;G. Steiner;Carlos Cordon-Cardo
酪氨酸激酶受体c-kit及其配体[kit配体（KL）或干细胞因子（SCF）]在器官发生和正常细胞发育过程中发挥广泛的生物活性。最近的研究表明，改变c-kit水平发生在各种恶性肿瘤和癌细胞系。KL还显示出刺激恶性细胞的生长，以及促进趋化性。我们以前曾报道KL在正常人前列腺基质细胞中的表达。本研究是为了分析c-kit和KL的表达模式，在一个良好的特征集的前列腺组织，包括正常前列腺（n=4），良性前列腺增生（BPH）（n=53）和腺癌（n=46）样品。通过免疫组织化学分析研究了c-kit和KL蛋白的分布，而转录水平通过在上述良性和恶性组织的一个子集上用特异性RNA探针进行原位杂交来确定。此外，进行逆转录酶聚合酶链反应（RT-PCR），以确定c-kit和KL的表达在上皮细胞和基质细胞的培养物，以及在前列腺癌细胞系LNCaP，DU 145和PC 3的水平。用免疫组化和原位杂交方法检测正常前列腺组织中c-kit蛋白仅见于肥大细胞。然而，c-kit转录本，而不是c-kit蛋白，检测到低水平和异质模式的导管和腺泡的基底上皮细胞。BPH组织中c-kit阳性率为17%（9/53）。在46例肿瘤中的1例（2%）中鉴定出恶性上皮细胞中的c-kit蛋白表达。然而，在大多数分析的肿瘤中，原位杂交检测到低水平的c-kit转录本。KL蛋白和转录本在正常前列腺基质细胞中呈高水平表达。然而，上皮细胞不反应的抗KL抗体，但表现出低水平的KL转录主要在基底层的细胞。53例增生腺体中13例（24%）基底上皮细胞表达KL。KL蛋白阳性率为39%（18/46）。RT-PCR检测正常前列腺组织和3种前列腺癌细胞系中均未发现c-kit基因的转录本，但在培养的BPH上皮细胞、正常前列腺组织和BPH间质细胞中均有c-kit基因的表达。大多数上皮和基质来源的培养细胞系显示相当高的KL水平。此外，研究的所有前列腺细胞系均显示显著水平的KL转录物。总之，c-kit和KL在BPH病例亚组中的共表达可能提示信号传导的自分泌模式。本研究的数据显示，c-kit和KL表达模式的改变与BPH和前列腺癌相关。KL诱导肥大细胞增殖和成熟，并促进其蛋白酶的释放。这可以解释肥大细胞在肿瘤部位的积累，这是在正常前列腺或BPH样本中没有观察到的现象。
The tyrosine kinase receptor c-kit and its ligand [kit ligand (KL) or stem cell factor (SCF)] exert a broad range of biological activities during organogenesis and normal cell development. Recent studies have revealed that altered c-kit levels occur in a variety of malignancies and cancer cell lines. KL has also been shown to stimulate the growth of malignant cells, as well as to promote chemotaxis. We had previously reported expression of KL in stroma cells of normal human prostate. The present study was undertaken in order to analyze the patterns of expression of c-kit and KL in a well characterized set of prostatic tissues, including normal prostate (n=4), benign prostatic hyperplasia (BPH) (n=53) and adenocarcinoma (n=46) samples. The distribution of c-kit and KL proteins was studied by immunohistochemical analyses, while transcript levels were determined by in situ hybridization with specific RNA probes on a subset of the benign and malignant tissues referred above. In addition, reverse-transcriptase polymerase chain reaction (RT-PCR) was performed to determine levels of c-kit and KL expression in cultures of epithelial and stroma cells, as well as in the prostate cancer cell lines LNCaP, DU145 and PC3. c-kit protein in normal prostate was exclusively detected in mast cells by immunohistochemistry and in situ hybridization. However, c-kit transcripts, but not c-kit protein, were detected in low levels and with an heterogeneous pattern in basal epithelial cells of ducts and acini. c-kit in BPH was detected in epithelial cells in 9 of 53 (17%) specimens. c-kit protein expression in malignant epithelial cells was identified in 1 of 46 (2%) tumors. However, c-kit transcripts were detected in low levels by in situ hybridization in most of the tumors analyzed. KL protein and transcripts in normal prostate were detected in high levels in stroma cells. However, epithelial cells were unreactive for anti-KL antibody, but showed low levels of KL transcripts mainly in cells of the basal layer. Basal epithelial cells in hyperplastic glands showed KL expression in 13 of 53 (24%) specimens. KL protein in tumor cells was noted in 18 of 46 (39%) cases. c-kit transcripts were not found in normal prostate and in the 3 cancer cell lines analyzed by RT-PCR, however, it was present in cultured epithelial cells of BPH, and in cultures of stroma cells from both normal and BPH. The majority of cultured cell lines of epithelial and stromal origin displayed considerable levels of KL. In addition all prostate cell lines studied showed significant levels of KL transcripts. In summary, co-expression of c-kit and KL in a subset of BPH cases may suggest an autocrine mode of signaling. Data from this study reveals that altered patterns of c-kit and KL expression are associated with BPH and adenocarcinoma of prostate. It appears that KL induces mast cells proliferation and maturation and enhances their release of protease. This could explain the accumulation of mast cells at tumor sites, a phenomenon that was not observed in normal prostate or BPH samples.