Leung H Y, Mehta P, Gray L B, Collins A T, Robson C N, Neal D E
Department of Surgery, The Medical School, University of Newcastle upon Tyne, UK.
Oncogene. 1997 Aug 28;15(9):1115-20. doi: 10.1038/sj.onc.1201256.
Cellular interactions between stroma and epithelium are important in the growth and proliferation of prostate cancer. Peptide growth factors may facilitate the progression of prostate cancer as autocrine and/or paracrine factors. Keratinocyte Growth Factor (KGF or FGF7) has a differentiative and proliferative effect on the epithelium of the developing rat prostate. We investigated if KGF may act as a paracrine agent in human prostate cancer and examined the expression of KGF and Fibroblast Growth Factor Receptors (FGFRs) (IIIb and IIIc isoforms of the FGFR1 and FGFR2 genes). Sixty-five percent (11 out of 17 informative cases) of prostate cancers (CaP) expressed KGF mRNA by RT-PCR, while KGF expression was not detected in benign prostatic hyperplasia (BPH) (n = 6). Upregulation of KGF expression was related to hormone insensitive tumours (P<0.05). Tumour grade and stage were not associated with KGF expression. The source of KGF expression was further characterised using an in vitro primary culture model, showing its restriction to the prostatic stroma. The FGFR1IIIb isoform was expressed in all cases of prostate cancer (n = 17), and FGFR1IIIc mRNA was not detected. In the BPH group, FGFR1IIIb transcripts were detected in four out of six cases. FGFR2IIIb expression was detected in five of six cases of BPH and twelve out of seventeen (71%) cases of prostate cancer. In CaP, though not reaching statistical significance, the persistence of FGFR2IIIb expression appeared to be associated with hormone insensitive tumours (P=0.052). FGFR2IIIc expression was present in eleven of seventeen tumours but was absent in all six cases of BPH. Functional assessment of recombinant KGF in a proliferation assay demonstrated a mitogenic effect of up to 100% on cultured prostatic epithelial cells.
基质与上皮细胞之间的细胞相互作用在前列腺癌的生长和增殖过程中起着重要作用。肽生长因子可能作为自分泌和/或旁分泌因子促进前列腺癌的进展。角质形成细胞生长因子（KGF或FGF7）对发育中的大鼠前列腺上皮具有分化和增殖作用。我们研究了KGF是否可能作为人前列腺癌中的旁分泌因子，并检测了KGF和成纤维细胞生长因子受体（FGFRs）（FGFR1和FGFR2基因的IIIb和IIIc亚型）的表达。通过逆转录聚合酶链反应（RT-PCR），65%（17例信息充分的病例中有11例）的前列腺癌（CaP）表达KGF mRNA，而在良性前列腺增生（BPH）（n = 6）中未检测到KGF表达。KGF表达上调与激素不敏感肿瘤相关（P<0.05）。肿瘤分级和分期与KGF表达无关。使用体外原代培养模型进一步表征了KGF表达的来源，表明其局限于前列腺基质。FGFR1IIIb亚型在所有前列腺癌病例（n = 17）中均有表达，未检测到FGFR1IIIc mRNA。在BPH组中，6例中有4例检测到FGFR1IIIb转录本。FGFR2IIIb表达在6例BPH中有5例检测到，在17例前列腺癌中有12例（71%）检测到。在CaP中，尽管未达到统计学意义，但FGFR2IIIb表达的持续存在似乎与激素不敏感肿瘤相关（P = 0.052）。FGFR2IIIc表达在17例肿瘤中有11例存在，但在所有6例BPH中均不存在。重组KGF在增殖试验中的功能评估表明，其对培养的前列腺上皮细胞具有高达100%的促有丝分裂作用。
