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Transforming Growth Factor‐β1 and Regulators of Apoptosis
Author(s) -
Sulkowski Stanislaw,
Wincewicz Andrzej,
Sulkowska Mariola,
Koda Mariusz
Publication year - 2009
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2009.04686.x
Subject(s) - transforming growth factor , apoptosis , cancer research , immunohistochemistry , biology , cancer cell , cytoplasm , transforming growth factor beta , colorectal cancer , cancer , immunology , microbiology and biotechnology , genetics
Growth inhibitory function of transforming growth factor‐β1 (TGF‐β1) is abolished in colorectal cancer cells as a consequence of mutations of various downstream signaling agents, such as p53, which fail to respond to TGF‐β1 stimulation. TGF‐β1 could also suppress T‐cell‐mediated anticancer immunity. We aimed at a comparison between cancer expressions of apoptosis regulators, such as p53, BCL‐2‐associated X protein (Bax), and B‐cell leukemia/lymphoma extra‐long protein (Bcl‐xL), with TGF‐β1 in malignant and adjacent inflammatory cells in immunohistochemical evaluations of 108 colorectal cancers. Cytoplasm compartment of cancer cells was overloaded with TGF‐β1, and 87% of all cancers were TGF‐β1 positive (94/108). A very strong pattern of staining was detected for TGF‐β1 in cytoplasm of inflammatory cells at tumor margins. TGF‐β1 correlated with Bcl‐xL and Bax in all colorectal cancers ( P < 0.001, r = 0.473 and P < 0.001, r = 0.435, respectively) and subgroups of different clinicopathological features, especially in deeply invading cancers (pT3+pT4) instead of superficially growing tumors (pT1+pT2). Expression of TGF‐β1 in inflammatory infiltrates correlated with immunoreactivities to Bcl‐xL of cancer cells ( P = 0.024, r = 0.217). TGF‐β1 did not associate with p53, nor did TGF‐β1 of inflammatory cells correlate with Bax expression in cancer cells. Lack of correlations between TGF‐β1 and p53 proteins could indicate mutations at the TGF‐β1‐dependent apoptotic pathway. Dominant positive linkage between TGF‐β1 and Bcl‐xL and selective lack of association with Bax suggest TGF‐β1 could support colorectal cancer cell survival. The pattern of correlations seems to confirm a remarkable shift from TGF‐β1‐dependent suppression of cancer growth by apoptosis to inhibition of anticancer immunity by TGF‐β1.