Mitogen-activated protein kinase (MAPK) pathways represent key signalling cascades that interfere with a broad range of cellular processes such as proliferation, differentiation, apoptosis and migration. These pathways are modulated by various mechanisms, including the negative-feedback regulators Sprouty1-4 (Spry1-4). Spry family members are known to have overlapping modes of action but their functions are not redundant. Spry proteins fulfill a central role in proliferative signalling and are frequently downregulated in diverse malignancies. Hence they are assumed to be tumor suppressors. Especially Spry2 expression is suppressed in many tumor entities including lung cancer. Since microRNA-21 (miR-21) was recently reported to target Spry2, we investigated the potential impact of miR-21 on Spry2 expression in lung cancer. In this thesis we analysed miR-21 levels in Non-small cell lung cancer (NSCLC)-derived tissue samples and cell lines. Consistent with earlier studies, the obtained results demonstrate that miR-21 is elevated in tumor versus normal lung tissue. Additionally we unveiled that with progression of the disease the increase of miR-21 is considerably more pronounced. As expected, lung tumor tissues with high miR-21 levels tended to express low Spry2 amounts. In contrast to the lung tumor tissues, NSCLC-derived cell lines exhibited miR-21 levels comparable to those of non-malignant tissues and cell lines. Accordingly, we found no correlation between miR-21 levels and Spry2 expression in NSCLC-derived cell lines. Nonetheless the observation that miR-21 was upregulated solely in the tissue context was particularly interesting since the data indicated that microenvironmental conditions, which are not mimicked in cell culture, play an important role in regulation of miR-21. Hence we studied the influence of tumor-associated environmental factors on miR-21. While the expression of miR-21 was not affected by cancer-associated fibroblasts, both oxygen withdrawal and anchorage-independent growth led to augmented miR-21 levels in NSCLC-derived cell lines. These results highlight that miR-21 is regulated by tissue-specific microenvironmental conditions rather than intrinsic factors. NSCLC-derived cells growing anchorage-independently or under hypoxia harboured reduced Spry2 levels, pointing to miR-21-mediated regulation of Spry2. In contrast to the data obtained for Spry2, evaluation of Spry4 expression under hypoxic conditions revealed that Spry4 is upregulated in diverse cell lines. The increase of Spry4 expression following iron deprivation was irrespective of cell origin, differentiation and malignancy. Moreover, this study uncovered a mitogen-independent regulation of Spry4. A detailed analysis of the underlying mechanisms showed that primarily enhanced mRNA stability and augmented transcriptional activity account for Spry4 enhancement, while Spry4 protein was destabilized upon iron withdrawal. Hypoxia-inducible factor-1, a main transcriptional regulator during hypoxia, was shown to be involved in Spry4 promoter control. Analysis of MAPK signalling illustrated that Spry4 presumably suppresses this pathway under hypoxic conditions, indicating that Spry4 contributes to the cellular adaption to hypoxia. In summary our data demonstrate that the expression of Spry proteins is controlled by distinct regulatory mechanisms in order to ensure appropriate availability of the different Spry protein family members.