The α6β4 integrin is a component of the hemidesmosome, the anchoring structure in the basal membrane of epithelial cells. α6β4 expression is frequently altered in neoplastic cells. It is sometimes lost and sometimes overexpressed, which suggests that disruption of normal function is involved in neoplastic transformation. To examine the effect of this integrin on the growth and behavior of malignant cells that have lost β4, we transfected a full-length β4 cDNA into the UM-UC-2 cell line that expresses α6 but not β4. Although large numbers of clones were obtained when a control vector was used in the transfection, only 12 clones could be isolated that expressed β4. Of these, only two β4-positive clones, clones 8 and 11, persisted long enough for further study. Clone 8 cells initially expressed β4, but within 2 weeks, all positive cells were lost from the culture. Clone 11 persisted inculture and retained strong surface expression of α6β4. Biochemical analysis and Western blotting revealed that this clone contained a truncated form of β4 that had lost the distal cytoplasmic domain. We conclude that expression of wild-type β4 in UM-UC-2 inhibits cell growth, presumably by an integrin-mediated signaling pathway. Clone 11 escaped from normal signaling because the cytoplasmic domain, a region essential for basal polar localization, was lost. The α6β4 integrin appears to have tumor suppressor activity in epithelial tumors.


Supported by grants from the Office of the Vice President for Research of the University of Michigan, the NIH-NCI CA56973 and NCI CA56973, the General Clinical Research Center Grant MO1-RR00042, and from the Asan Medical Center and Asan Institute for Life Science.

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