Human gastric glandular epithelium produces a gastric lipase enzyme (HGL) which plays an important role in digestion of dietary triglycerides. In order to assess the involvement of extracellular matrix components and transforming growth factor-ß1 (TGFß1) in the regulation of this enzymic function, normal gastric epithelial cells were cultured on collagen-I, Matrigel and laminins-1,-2 (LNs) with or without TGFß1. Epithelial morphology as well as HGL expression were evaluated using microscopy techniques, enzymic assays, Western blot, Northern hybridization and RT-PCR. A correlation was observed between the cell polarity status and the level of HGL expression. TGFß1 alone or individual matrix components stimulated cell spreading and caused a downfall of HGL activity and mRNA. By contrast, Matrigel preserved the morphological features of differentiated epithelial cells and maintained HGL expression. The combination of LNs with TGFß1 (two constituents of Matrigel) exerted similar beneficial effects on epithelial cell polarity and evoked a ten-fold increase of HGL that was blunted by a neutralizing antibody against the 2-integrin subunit and by MAPK inhibitors PD98059 (p42/p44) or SB203580 (p38). This investigation demonstrates for the first time that a powerful synergism between a growth factor and basement membrane LNs positively influences cell polarity and functionality of the human gastric glandular epithelium through an activation of the 2ß1 integrin and effectors of two MAPK pathways.