PubMed · 368546
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
G E Feurle. 1979-02-02. [Gastrointestinal hormones. Current knowledge].. https://pubmed.ncbi.nlm.nih.gov/368546/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
At least 70% of small cell lung cancer (SCLC) tumors and tumor-derived cell lines coexpress the genes for stem cell factor (SCF) and its receptor, the c-kit proto-oncogene. To assess the impact of coexpression of the growth factor and receptor on SCLC growth, the NCI-H146 SCLC cell line, which expresses only SCF, was transfected with a c-kit expression vector. Kit protein immunoprecipitated from the transfected cells had a constitutive level of tyrosine phosphorylation, and these cells grew more vigorously in serum-free medium compared to control-transfected cells. This growth advantage could be blocked by the addition of the tyrosine kinase inhibitor herbimycin A. Growth of the c-kit-transfected cells could be further enhanced by the addition of bombesin or insulin-like growth factor-1, suggesting that the SCF/c-kit autocrine loop could function cooperatively with other SCLC autocrine loops. To further investigate the importance of this autocrine loop, a cell line that naturally coexpresses SCF and c-kit was transfected with a kinase-defective c-kit gene. Cells transfected with the defective gene showed a marked decrease in their ability to grow under growth factor-free conditions compared to cells transfected with the empty expression vector. Taken together, these studies demonstrate that the coexpression of the stem cell factor and c-kit genes is a major contributor to the growth factor independence of SCLC.
There is an intriguing link between differentiation of neuroendocrine cells and tumor progression in prostate cancer. Neuroendocrine differentiation appears to be associated with the androgen-independent state, for which there is currently no successful therapy. However, the role of the neuroendocrine cells is complex, both in the normal prostate and in the pathway toward malignancy. One important area of research is to investigate the hormones expressed by prostatic neuroendocrine cells and, in particular, to elucidate their significance to androgen independence. It is hoped that an understanding of the specific roles of hormones such as somatostatin, bombesin, and serotonin in prostate cancer may lead to improved therapeutic approaches.
The effects of bombesin/gastrin-releasing peptide (BN/GRP) on c-fos and c-jun gene expression were investigated using small cell lung cancer (SCLC) cells. BN (10 nM) increased c-fos mRNA fivefold using NCI-H345 or NCI-H510 cells. The increase was concentration dependent with 1 nM BN half-maximally increasing c-fos mRNA. Also, the increase in c-fos mRNA caused by BN was time dependent, being maximal after 1 h and returning to basal values after 4 h. GRP and GRP(14-27) but not GRP(1-16) increased c-fos mRNA. BW2258U89 (1 microM), a GRP receptor antagonist, had no effect on basal c-fos but inhibited the increase in c-fos mRNA caused by 10 nM BN. Also, BN transiently increased c-jun mRNA twofold and the increase caused by BN was blocked by BW2258U89. These data suggest that GRP receptors may regulate nuclear oncogene gene expression in SCLC cells.