Increases in c-Src expression level and activity do not promote the growth of human colorectal carcinoma cells in vitro and in vivo.
The levels and activity of c-Src in colorectal cancer cells increase steadily during the course of colorectal carcinogenesis and are most highly elevated in advanced metastatic disease. However, the effects of increases in c-Src activity on the proliferation of colorectal cancer cells during early and late stages of tumorigenesis remain elusive. To study the consequences of increases in c-Src levels and activity on the growth of colorectal cancer cells in later stages of colorectal carcinogenesis, we developed human colorectal cancer cell lines in which c-Src levels and activity could be inducibly increased by a tightly controlled expression of wild-type c-Src or of the constitutively active mutant of c-Src, c-SrcY527F. Src induction activated multiple signaling pathways (often associated with a proliferative response) but promoted neither cell proliferation in vitro nor tumor growth in a xenograft model in vivo. These results indicate that, in more advanced stages of colorectal carcinogenesis, increases in c-Src levels and activity are likely to have functions other than the direct promotion of tumor growth.
Welman
Arkadiusz
A
Clinical and Experimental Pharmacology Group, Cancer Research UK, Paterson Institute for Cancer Research, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK. awelman@picr.man.ac.uk
Cawthorne
Christopher
C
Ponce-Perez
Lourdes
L
Barraclough
Jane
J
Danson
Sarah
S
Murray
Stephen
S
Cummings
Jeff
J
Allen
Terry D
TD
Dive
Caroline
C
D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004318:Doxycycline / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D008954:Models, Biological; D009368:Neoplasm Transplantation; D019061:src-Family Kinases / Q000096:biosynthesis*
D019061:src-Family Kinases; D004318:Doxycycline