Marengo S R, Chung L W
Urology Research Laboratory, University of Texas M.D. Anderson Cancer Center, Houston 77030.
J Androl. 1994 Jul-Aug;15(4):277-86.
In order to determine if epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) are capable of stimulating prostatic growth in situ, we complexed EGF and bFGF to a Matrigel (MG) vehicle that was subsequently injected orthotopically into the ventral prostate of adult rats. Three weeks following a single injection of 0.1 ng of EGF or bFGF, the wet weight of the growth factor-injected lobes of the ventral prostate was increased (P < or = 0.025) 144 +/- 14% and 138 +/- 8%, respectively compared to contralateral lobes injected with MG only. Total DNA and protein per lobe (P < or = 0.025) and the incorporation of bromodeoxyuridini (BrdUrd; P < or 0.01) were all significantly increased in lobes injected with EGF or bFGF compared to MG-injected lobes. Thus, EGF and bFGF were stimulating true growth of the rat ventral prostate in situ. The induced prostatic growth was ligand specific, because co-injection with neutralizing antibodies abolished EGF and bFGF stimulation of prostatic wet weight. The effect of a single injection of 0.1 ng of growth factor was long-lasting and elevated prostatic wet weight for 4 (P < or = 0.05; bFGF) to 6 (P < or = 0.05; EGF) weeks. Histologic evaluation did not reveal any gross changes in the ratio of stroma to epithelium in either EGF- or bFGF-injected lobes at the 0.1 ng/lobe dose. A slight hyperplasia of the prostatic epithelium was detected in lobes injected with 10 ng of EGF. Of note, the incorporation of BrdUrd was primarily localized in the luminal and basal epithelial cells, whereas incorporation into the prostatic stroma was scanty in lobes injected with either EGF or bFGF. In summary, we have developed an orthotopic model enabling the study of the roles of growth factors in prostatic physiology, function, and disease in situ. Additionally, we have demonstrated that when injected orthotopically into the rat ventral prostate, EGF and bFGF stimulate the growth of the prostatic epithelium to similar degrees.
为了确定表皮生长因子（EGF）或碱性成纤维细胞生长因子（bFGF）是否能够原位刺激前列腺生长，我们将EGF和bFGF与基质胶（MG）载体复合，随后将其原位注射到成年大鼠的腹侧前列腺中。单次注射0.1 ng EGF或bFGF三周后，与仅注射MG的对侧叶相比，注射生长因子的腹侧前列腺叶的湿重分别增加了144±14%和138±8%（P≤0.025）。与注射MG的叶相比，注射EGF或bFGF的叶中每叶的总DNA和蛋白质（P≤0.025）以及溴脱氧尿苷（BrdUrd）的掺入量（P＜0.01）均显著增加。因此，EGF和bFGF正在原位刺激大鼠腹侧前列腺的真正生长。诱导的前列腺生长具有配体特异性，因为与中和抗体共同注射可消除EGF和bFGF对前列腺湿重的刺激。单次注射0.1 ng生长因子的作用是持久的，前列腺湿重增加了4周（P≤0.05；bFGF）至6周（P≤0.05；EGF）。组织学评估未发现以0.1 ng/叶剂量注射EGF或bFGF的叶中基质与上皮比例有任何明显变化。在注射10 ng EGF的叶中检测到前列腺上皮有轻微增生。值得注意的是，BrdUrd的掺入主要定位于管腔和基底上皮细胞，而在注射EGF或bFGF的叶中，前列腺基质中的掺入量很少。总之，我们开发了一种原位模型，能够研究生长因子在前列腺生理、功能和疾病中的作用。此外，我们已经证明，当原位注射到大鼠腹侧前列腺中时，EGF和bFGF对前列腺上皮生长的刺激程度相似。
