ABSTRACT
Renal cell carcinoma (RCC) is the most frequent cancer of the kidney and it accounts for 3% of all solid malignancies. Although rare, cutaneous metastases can be an important manifestation of RCC. We present a case of a 56-year-old male with a history of RCC, followed by the development of cutaneous metastases 4 years later with an uncommon clinical presentation. RCC is the most common genitourinary cancer to metastasize to the skin and accounts for 6.8% of cutaneous metastases. These patients have a poor prognosis. It is essential for these patients to perform a complete periodic dermatologic examination for proper restaging and treatment.
ABSTRACT
IGF-1 is one of the key molecules in cancer biology; however, little is known about the role of the preferential expression of the premature IGF-1 isoforms in prostate cancer. We have examined the role of the cleaved COO- terminal peptide (PEc) of the third IGF-1 isoform, IGF-1Ec, in prostate cancer. Our evidence suggests that endogenously produced PEc induces cellular proliferation in the human prostate cancer cells (PC-3) in vitro and in vivo, by activating the ERK1/2 pathway in an autocrine/paracrine manner. PEc overexpressing cells and tumors presented evidence of epithelial to mesenchymal transition, whereas the orthotopic injection of PEc-overexpressing, normal prostate epithelium cells (HPrEC) in SCID mice was associated with increased metastatic rate. In humans, the IGF-1Ec expression was detected in prostate cancer biopsies, where its expression correlates with tumor stage. Our data describes the action of PEc in prostate cancer biology and defines its potential role in tumor growth, progression and metastasis.
Subject(s)
Insulin-Like Growth Factor I/metabolism , Peptides/metabolism , Prostatic Neoplasms/metabolism , Animals , Autocrine Communication , Biopsy , Cell Line, Tumor , Cell Proliferation , Disease Models, Animal , Epithelial-Mesenchymal Transition , Gene Expression , Heterografts , Humans , Insulin-Like Growth Factor I/chemistry , Insulin-Like Growth Factor I/genetics , Male , Mice , Mice, SCID , Models, Biological , Neoplasm Metastasis , Paracrine Communication , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Protein IsoformsABSTRACT
BACKGROUND: Heterogeneous nuclear ribonucleoproteins (hnRNPs) of the A/B type (hnRNP A1, A2/B1, A3) are highly related multifunctional proteins participating in alternative splicing by antagonising other splicing factors, notably ASF/SF2. The altered expression pattern of hnRNP A2/B1 and/or splicing variant B1 alone in human lung cancer and their potential to serve as molecular markers for early diagnosis remain issues of intense investigation. The main objective of the present study was to use paired tumour/non-tumour biopsies from patients with non-small cell lung cancer (NSCLC) to investigate the expression profiles of hnRNP A1, A2/B1 and A3 in conjunction with ASF/SF2. METHODS: We combined western blotting of tissue homogenates with immunohistochemical examination of fixed tissue sections and quantification of mRNA expression levels in tumour versus adjacent normal-looking areas of the lung in the same patient. RESULTS: Our study, in addition to clear evidence of mostly uncoupled deregulation of hnRNPs A/B, has revealed hnRNP A1 to be the most deregulated protein with a high frequency of over-expression (76%), followed by A3 (52%) and A2/B1 (43%). Moreover, direct comparison of protein/mRNA levels showed a lack of correlation in the case of hnRNP A1 (as well as of ASF/SF2), but not of A2/B1, suggesting that different mechanisms underlie their deregulation. CONCLUSION: Our results provide strong evidence for the up-regulation of hnRNP A/B in NSCLC, and they support the existence of distinct mechanisms responsible for their deregulated expression.
