R.A.S HEMAT, MB;BCh, FRCSI, DUL.
Peptide growth factors (PGFs) are hormones interact with cell receptors, setting a motion of cascade of intracellular events that either turn on or turn off assorted subsets of genes that govern the cell's response to injury and that mediate the highly coordinated processes of cell growth, differentiation and apoptosis. If the cell responds to the same peptide growth factor that it is simultaneously producing, it is using an autocrine pathway. A paracrine pathway is utilised when one cell type elaborates a PGF but a different cell type responds to it.
There are 6 major growth factors family:
1- Insulin and insulin-like growth factor (IGF-I, IGFBPs).
2- Nerve growth factor (NGF).
3- Platelet-derived growth factor (PDGF).
4- Epidermal growth factor (EGF).
5-Transforming growth factor-beta (TGFb).
6- Heparin-binding growth factor.
EGFR expression increases nuclear size and tumour dedifferentiation. EGF and TGFa are polypeptide growth factors that interact with cell-surface EGFR.
The normal prostate expresses higher level of EGF than TGFa. EGFR has shown high level of expression in NE cells. Castration results in an increase in EGFR content per gram of tissue and may reflect the survival of androgen-insensitive and EGFR-enriched basal/NE cells after androgen ablation.
During the phase of bladder response (hypertrophy), there is a dramatic increase in the bladder's expression of bFGF in conjunction with a decrease in the bladder's endogenous expression of TGF-b. The stretched urothelial lining in an overdistended bladder would be regenerated when an effective growth factor (EGF) in the urine was able to penetrate to the deepest layer of this tissue and stimulate the regrowth of a barrier layer of urothelial cells. There is a rapid increase in bladder mass up to ten-fold following partial outlet obstruction, which is the result of both smooth muscle cell hypertrophy and hyperplasia of cells in the inner (urothelium) and outer (serosa) lining of the bladder.
The concentration of EGFR in bladder cancer increases as the invasiveness and the grade of the TCC increase. Higher levels of EGFR are associated with recurrence and progression in low-stage bladder cancer. Normal urothelium express Transferrin receptor limited to basal cells, increasing expression of transferrin receptor is noted with both increasing stage and grade.
Reduced levels of TGF-b1 mRNA have been associated with bladder tumour recurrence and progression and may represent a useful prognostic marker.
August, 2001
Note: The information in this article has been excerpted from the following books: urotext-ebook simplifying urology, Principles of modern urology, by Dr. R.A.S HEMAT. Permission is granted to copy and redistribute this document electronically as long as it is unmodified. This article may not be sold in any medium, including electronic, CD-ROM, or database, or published in print, without the explicit, written permission of Dr. R. A. S. Hemat.
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Dr. R.A.S HEMAT declares no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, stock holdings, gifts, or honoraria.
