Biomaterial Database

Growth factor regulation of gene expression in the human prostatic carcinoma cell line LNCaP. 1993

P Henttu, and P Vihko

Biocenter, University of Oulu, Finland.

In order to characterize the effects of growth factors on the regulation of expression of the genes coding for prostatic differentiation markers, prostatic acid phosphatase and prostate-specific antigen, we studied changes occurring in the biosynthesis of these enzymes in LNCaP prostatic cancer cells treated with growth factors. Epidermal growth factor was found to reduce the secretion of prostatic acid phosphatase and prostate-specific antigen by the cells, as the result of lowered steady-state levels of the corresponding messenger RNAs (mRNAs). In addition, epidermal growth factor (EGF) interfered with the androgen regulation of these genes. EGF evoked these changes in a concentration- and time-dependent fashion, in both the presence and absence of serum and most likely through interactions with the epidermal growth factor receptor, inasmuch as similar effects were achieved by treating the cells with transforming growth factor alpha. The regulation of the human glandular kallikrein 1 gene was quite similar to the regulation of the prostate-specific antigen gene. In addition to the expression of the genes coding for prostatic secretory proteins, the amount of the human androgen receptor mRNA was down-regulated by EGF. This reduction was more pronounced than the autologous down-regulation of human androgen receptor (hAR) mRNA by androgen and could be maintained for at least 5 days. In the presence of androgen, some of the effects of EGF and transforming growth factor alpha on the levels of androgen-regulated mRNAs may be due to down-regulation of the expression of the hAR gene. Transforming growth factor beta 1, which blocked the growth induction of LNCaP cells by EGF, increased the level of prostatic acid phosphatase and hAR mRNAs, but when given to the cells together with EGF its up-regulatory effect could not be discerned. In summary, regulation of the prostatic acid phosphatase and prostate-specific antigen genes is a complex matter, inasmuch as androgens and growth factors regulate the levels of the mRNAs originating from them. Furthermore, the interactions between the androgen-regulatory system and the growth factor-regulatory systems are likely to be at multiple levels in prostatic cells, as suggested by the modulation of the hAR gene expression by these growth factors.

UI	MeSH Term	Description	Entries
D007610	Kallikreins	Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, PLASMA KALLIKREIN (EC 3.4.21.34), TISSUE KALLIKREIN (EC 3.4.21.35), and PROSTATE-SPECIFIC ANTIGEN (EC 3.4.21.77).	Kallikrein,Kininogenase,Callicrein,Dilminal,Kallidinogenase,Kalliginogenase,Kallikrein A,Kallikrein B',Kallikrein Light Chain,Kinin-Forming Enzyme,Padutin,alpha-Kallikrein,beta-Kallikrein,beta-Kallikrein B,Enzyme, Kinin-Forming,Kinin Forming Enzyme,Light Chain, Kallikrein,alpha Kallikrein,beta Kallikrein,beta Kallikrein B
D008297	Male		Males
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011471	Prostatic Neoplasms	Tumors or cancer of the PROSTATE.	Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D011944	Receptors, Androgen	Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.	Androgen Receptors,5 alpha-Dihydrotestosterone Receptor,Androgen Receptor,Dihydrotestosterone Receptors,Receptor, Testosterone,Receptors, Androgens,Receptors, Dihydrotestosterone,Receptors, Stanolone,Stanolone Receptor,Testosterone Receptor,5 alpha Dihydrotestosterone Receptor,Androgens Receptors,Receptor, 5 alpha-Dihydrotestosterone,Receptor, Androgen,Receptor, Stanolone,Stanolone Receptors,alpha-Dihydrotestosterone Receptor, 5
D002277	Carcinoma	A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for "cancer."	Carcinoma, Anaplastic,Carcinoma, Spindle-Cell,Carcinoma, Undifferentiated,Carcinomatosis,Epithelial Neoplasms, Malignant,Epithelioma,Epithelial Tumors, Malignant,Malignant Epithelial Neoplasms,Neoplasms, Malignant Epithelial,Anaplastic Carcinoma,Anaplastic Carcinomas,Carcinoma, Spindle Cell,Carcinomas,Carcinomatoses,Epithelial Neoplasm, Malignant,Epithelial Tumor, Malignant,Epitheliomas,Malignant Epithelial Neoplasm,Malignant Epithelial Tumor,Malignant Epithelial Tumors,Neoplasm, Malignant Epithelial,Spindle-Cell Carcinoma,Spindle-Cell Carcinomas,Tumor, Malignant Epithelial,Undifferentiated Carcinoma,Undifferentiated Carcinomas
D004815	Epidermal Growth Factor	A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.	EGF,Epidermal Growth Factor-Urogastrone,Urogastrone,Human Urinary Gastric Inhibitor,beta-Urogastrone,Growth Factor, Epidermal,Growth Factor-Urogastrone, Epidermal,beta Urogastrone
D005786	Gene Expression Regulation	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.	Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000135	Acid Phosphatase	An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2.	Acid beta-Glycerophosphatase,Acid beta Glycerophosphatase