BACKGROUND AND AIMS: The mesenchymal derived keratinocyte growth factor stimulates growth, differentiation and migration of intestinal epithelial cells. In the human gastrointestinal tract an overexpression of this growth factor has been reported in inflammatory bowel disease and pancreatic cancer. In the present study we investigated expression patterns of keratinocyte growth factor and receptor in normal and neoplastic colonic mucosa and in metastases. Furthermore, biological effects on normal intestinal and colorectal cancer cell lines were determined. MATERIALS AND METHODS: Expression patterns were analysed at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. Localization of ligand and receptor in normal intestinal mucosa and cancer tissue was investigated by immunohistochemistry. Mitogenic effects of keratinocyte growth factor were assayed by [3H]thymidine incorporation in normal (Intestine-407, IEC-6, IEC-18) and colorectal cancer cell lines (Colo320, LoVo, SW403, SW707). RESULTS: mRNA expression of keratinocyte growth factor and receptor was detected in the majority of normal and cancer samples without significant alterations. At the protein level keratinocyte growth factor expression did not differ between normal and malignant specimens, whereas protein expression of the receptor was increased up to twofold in well- to moderately differentiated colorectal cancers. DNA synthesis was significantly stimulated by keratinocyte growth factor in all three normal intestinal cell lines, whereas this growth factor did not significantly alter the [3H]thymidine incorporation in the colorectal cancer cell lines. CONCLUSION: Keratinocyte growth factor and its receptor were detected in the majority of samples from normal and neoplastic colonic mucosa, with an overexpression of the receptor seen in the more differentiated tumour samples. Keratinocyte growth factor is a strong mitogen for normal intestinal cells, whereas it is less effective in neoplastic cells.
BACKGROUND AND AIMS: The mesenchymal derived keratinocyte growth factor stimulates growth, differentiation and migration of intestinal epithelial cells. In the human gastrointestinal tract an overexpression of this growth factor has been reported in inflammatory bowel disease and pancreatic cancer. In the present study we investigated expression patterns of keratinocyte growth factor and receptor in normal and neoplastic colonic mucosa and in metastases. Furthermore, biological effects on normal intestinal and colorectal cancer cell lines were determined. MATERIALS AND METHODS: Expression patterns were analysed at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) and at the protein level by Western blotting. Localization of ligand and receptor in normal intestinal mucosa and cancer tissue was investigated by immunohistochemistry. Mitogenic effects of keratinocyte growth factor were assayed by [3H]thymidine incorporation in normal (Intestine-407, IEC-6, IEC-18) and colorectal cancer cell lines (Colo320, LoVo, SW403, SW707). RESULTS: mRNA expression of keratinocyte growth factor and receptor was detected in the majority of normal and cancer samples without significant alterations. At the protein level keratinocyte growth factor expression did not differ between normal and malignant specimens, whereas protein expression of the receptor was increased up to twofold in well- to moderately differentiated colorectal cancers. DNA synthesis was significantly stimulated by keratinocyte growth factor in all three normal intestinal cell lines, whereas this growth factor did not significantly alter the [3H]thymidine incorporation in the colorectal cancer cell lines. CONCLUSION: Keratinocyte growth factor and its receptor were detected in the majority of samples from normal and neoplastic colonic mucosa, with an overexpression of the receptor seen in the more differentiated tumour samples. Keratinocyte growth factor is a strong mitogen for normal intestinal cells, whereas it is less effective in neoplastic cells.
Authors: Andrew Woolston; Khurum Khan; Georgia Spain; Louise J Barber; Beatrice Griffiths; Reyes Gonzalez-Exposito; Lisa Hornsteiner; Marco Punta; Yatish Patil; Alice Newey; Sonia Mansukhani; Matthew N Davies; Andrew Furness; Francesco Sclafani; Clare Peckitt; Mirta Jiménez; Kyriakos Kouvelakis; Romana Ranftl; Ruwaida Begum; Isma Rana; Janet Thomas; Annette Bryant; Sergio Quezada; Andrew Wotherspoon; Nasir Khan; Nikolaos Fotiadis; Teresa Marafioti; Thomas Powles; Stefano Lise; Fernando Calvo; Sebastian Guettler; Katharina von Loga; Sheela Rao; David Watkins; Naureen Starling; Ian Chau; Anguraj Sadanandam; David Cunningham; Marco Gerlinger Journal: Cancer Cell Date: 2019-07-08 Impact factor: 31.743
Authors: Anita L Bane; Dushanthi Pinnaduwage; Sarah Colby; Michael Reedijk; Sean E Egan; Shelley B Bull; Frances P O'Malley; Irene L Andrulis Journal: Breast Cancer Res Treat Date: 2008-06-18 Impact factor: 4.872