p27 cell‐cycle inhibitor is inversely correlated with lymph node metastases in right‐sided colon cancer

Abstract

p27, a cyclin-dependent kinase inhibitor, suppresses proliferation of normal and neoplastic cells. Expression of p27 is correlated with survival in colon cancer. To some degree, right-sided colon cancers differ biologically and clinically from left-sided colon cancers. We analyzed 41 patients with right-sided colon cancers, including 18 cases with regional lymph node metastases and 23 cases with negative lymph nodes. Immunostaining for p27 was performed on histologic sections of primary cancers and scored. Correlation of p27 protein expression with histologic parameters was performed by t-test and multivariate analysis. Decreased p27 protein expression was associated with large tumor size. As percentages of positively stained tumor cells decreased from 70 to 29%, the mean tumor size increased from 1.9 to 7.3 cm. p27 protein expression significantly decreased in primary cancers with angiolymphatic invasion or with positive lymph nodes in comparison with those without angiolymphatic invasion (26 +/- 6 vs. 44 +/- 5%, P < 0.03) or with negative lymph nodes (23 +/- 4 vs. 47 +/- 6%, P < 0.003). p27 expression was not statistically different in terms of depth of tumor invasion (T1/T2 vs. T3/T4), tumor type or tumor differentiation. Multivariate analysis revealed that low p27 expression in primary cancers was correlated with lymph node metastases (P = 0.01). However, it did not correlate with any other histologic parameters. In summary, decreased p27 expression was associated with an increased likelihood of lymph node metastases in colon cancers, independent of depth of tumor invasion. This implies that p27 is a potentially important predictor for tumor metastasis and patient's prognosis in right-sided colon cancers.

Down-Regulation of the Mammalian Target of Rapamycin (mTOR) Pathway Mediates the Effects of the Paeonol-Platinum(II) Complex in Human Thyroid Carcinoma Cells and Mouse SW1736 Tumor Xenografts

“…A previous study showed an inverse association between PI3K/mTOR activation and p27 expression, and targeting this pathway promoted the expression of p27 [45]. The down-regulation of mTORC1 dephosphorylates 4E-BP1, followed by its binding to eIF4E, which blocks protein translation and cell proliferation [42,43]. The findings from the present study showed upregulation of p27 and down-regulation of p-S6 in SW1736 and BHP7-13 cells treated with PL-Pt(II).…”

“…These findings supported the anti-proliferative activity of PL-Pt(II) for thyroid cancer cells by targeting the PI3K/ mTOR pathway. The activation of mTORC1 induces expression of S6 ribosomal protein, which is a downstream component of the S6 kinase 1 [41][42][43]. The p-S6 protein phosphorylation promotes the translation of proteins that increase the growth of cells.…”

In vitro differentiation of HT‐29 M6 mucus‐secreting colon cancer cells involves a trychostatin A and p27KIP1‐inducible transcriptional program of gene expression

“…The involvement of p27 KIP1 in colon tumor progression has been revealed in mice carrying the heterozygous or homozygous ablations of the p27 KIP1 gene (Moser et al, 1990; Fero et al, 1996; Philipp‐Staheli et al, 2002; Yang et al, 2003). Moreover, downregulation of p27 KIP1 protein levels or its altered subcellular location is becoming a reliable prognostic predictor for advanced disease and poor patient survival in colorectal carcinoma (Liu et al, 1999; Sgambato et al, 1999; Hoos et al, 2002; Li et al, 2002; Hershko and Shapira, 2006, and references therein). Therefore, loss of p27 KIP1 function appears to play a major role during tumor progression.…”