Growth stimulation of colorectal carcinoma cells via the c-kit receptor is inhibited by TGF-beta 1

J Cell Physiol. 1997 Jul;172(1):1-11. doi: 10.1002/(SICI)1097-4652(199707)172:1<1::AID-JCP1>3.0.CO;2-S.


Activation of the receptor tyrosine kinase c-kit by the kit-ligand, also known as stem cell factor (SCF), is essential to melanocyte and germ cell development and during the early stages of hematopoiesis. Deregulated expression of c-kit has been reported in malignancies affecting these lineages, i.e., myeloid leukemias, melanomas, and germ cell tumors. In addition, c-kit and SCF are coexpressed in some breast and colorectal cancer (CRC) cells, raising the question of whether c-kit serves an autocrine role in normal or malignant epithelial tissues. In this study, we demonstrate that human colorectal carcinomas, but not normal colorectal mucosa cells, coexpress SCF and c-kit in situ. Expression of c-kit was also observed in mucosa adjacent to colorectal tumor tissue. Consistent with a growth-regulatory role of SCF in CRC cells, exogenous SCF stimulated anchorage-dependent and anchorage-independent growth in four out of five CRC cell lines. Exogenous transforming growth factor (TGF)-beta 1 added at nanomolar concentrations to HT-29 CRC cells, which express the type I, II, and III TGF-beta receptors, downregulated c-kit expression to background levels and inhibited c-kit-dependent proliferation. Similarly, TGF-beta 1 inhibited SCF-dependent proliferation of three first-passage CRC cell lines. In summary, expression of the potential autocrine SCF/ c-kit axis is a tumor-associated phenomenon in colorectal cancer that can be suppressed by TGF-beta 1 in TGF-beta-responsive CRC cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Carcinoma / pathology*
  • Cell Adhesion
  • Cell Division
  • Colorectal Neoplasms / pathology*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intestinal Mucosa / metabolism
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins c-kit / physiology*
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Stem Cell Factor / physiology*
  • Transforming Growth Factor beta / pharmacology*


  • RNA, Messenger
  • RNA, Neoplasm
  • Stem Cell Factor
  • Transforming Growth Factor beta
  • Proto-Oncogene Proteins c-kit