Ubiquitin fusion proteins are overexpressed in colon cancer but not in gastric cancer

Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Biochimica et Biophysica Acta (Impact Factor: 4.66). 01/1996; 1272(3):147-53. DOI: 10.1016/0925-4439(95)00079-8
Source: PubMed


A cDNA clone (AF3) encoding the ubiquitin A gene 52 amino acid extension fusion protein (UbA52) was isolated from a subtracted cDNA library of human colorectal carcinoma minus adjacent normal mucosa. In Northern hybridization the mRNA signal for UbA52 was greater in surgical samples of colonic carcinoma (T) than in paired adjacent normal (N) tissues in 24 of 29 cases (T/N = 3.4 +/- 0.5, P < 0.01). An oligonucleotide probe specific for only the 52 amino acid extension confirmed the overexpression of UbA52. In contrast, there was no overexpression of UbA52 mRNA in gastric cancer samples (n = 7, T/N = 1.0 +/- 0.3). The mRNA of several ribosomal proteins, and of another ubiquitin A gene fusion protein, UbA80, with an 80 amino acid extension of ribosomal protein S27a, have been reported to be over-expressed in colon cancer, but not as yet at the protein level. Using rabbit antisera to the ribosomal protein component S27a we demonstrate over-expression of S27a at the protein level in colonic (n = 5), but not gastric (n = 6) carcinomas. Therefore it is likely that both UbA80 and UbA52 are overexpressed in colon cancer, but not in gastric cancer.

Full-text preview

Available from:
  • [Show abstract] [Hide abstract]
    ABSTRACT: Human metallopanstimulin (MPS-1) is a 9.4-kDa multifunctional ribosomal S27 nuclear "zinc finger" protein which is expressed in a wide variety of actively proliferating cells and tumor tissues. In this paper, we present a case of overexpression of MPS-1 in colon cancer tissues of a seventeen year old male. Biopsies at the anastomosis and adjacent normal colonic mucosa were obtained by colonoscopy twelve months after right hemicolectomy for an ascending colon well differentiated adenocarcinoma. Immunohistochemical localization of MPS-1 protein was performed by using specific anti-MPS-1 antibodies directed against the N-terminal region of this protein. Immunohistochemistry demostrated an overexpression of MPS-1 in colonic mucosa crypts in the samples obtained at the anastomosis. In contrast, no expression of MPS-1 was observed in the adjacent normal mucosa. Histopathology performed with hematoxilin and eosin staining revealed focal crypt distortion and proliferation, but no carcinoma. In this case, the overexpression of MPS-1 was a more definitive evidence of malignant transformation than histology, as demonstrated by the clinical course of the disease. The results support the hypothesis that increased levels of tissue MPS-1 may correlate with a more aggressive behavior of colon malignancy.
    No preview · Article · Jan 1997 · Anticancer research
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have previously shown that human metallopanstimulin (MPS-1) is a 9.4-kDa multifunctional ribosomal S27/nuclear "zinc finger" protein which is expressed in a wide variety of actively proliferating cells and tumor tissues. Furthermore, we have shown that detection of MPS-N immunoreactive material in sera corresponding to the NH2 terminus of MPS-1 provides a method for determining the presence of certain types of abnormal proliferative conditions and/or active oncogenic processes in patients. In this study, we investigated MPS-N and MPS-N-like antigens present in the blood of patients with prostatic carcinoma (PC) and their relationship to the clinical status of patients with PC. The presence of MPS-N immunoreactive material was determined using a sensitive and specific radioimmunoassay (RIA) which has been developed to measure circulating levels of MPS-N antigen(s). In addition, MPS-N levels were compared to the primary bio-marker used in PC patient management, Prostatic Specific Antigen (PSA). MPS-N concentrations were determined in the blood of 107 males having no evidence of PC, and in 126 patients diagnosed with PC. In patients, not having PC the MPS-N levels were lower than 10 ng/mL. In untreated patients having PC stages T1/T2, the MPS-N level range was 10-30 ng/mL; in stages T3/T4 the MPS-N level range was 30-50 ng/mL; and in stage Mlb (distant metastasis to the bones) the MPS-N levels were extremely high (> 50 ng/mL). In Mlb patients that did not respond to therapy, the MPS-N levels remained very high (> 50 ng/mL). In Mlb patients that went into remission after treatment, the MPS-N levels were dramatically reduced. In addition, a comparison of the test properties of MPS-N and PSA for prostate cancer were evaluated in a total of 231 patients. In both the low and high value range, both MPS-N and PSA appear to be equally effective in modifying the probability of the target condition-prostatic cancer. These findings show that (1) in untreated PC patients, the increase in serum MPS-N correlated with the stage of the disease; (2) MPS-N tumor marker predicted the degree of aggressiveness of tumor growth and response to therapy. In summary, despite the uncertainties of the relative contributions of the molecules being measured in cancer patients (authentic MPS-1, and MPS-N-like protein sequences), the MPS-N test is a pragmatic test that correlates well with active prostatic malignancy.
    No preview · Article · Jan 1997 · Anticancer research
  • [Show abstract] [Hide abstract]
    ABSTRACT: Glyceraldehyde-3-phosphate dehydrogenase (G3PDH) is often used as a control gene for mRNA expression, however it has been proposed to be overexpressed in all hepatocellular carcinomas (HCC). Equal amounts of tumor and paired normal (T/N) RNA, based on OD260/280 nm, were compared using ethidium bromide staining, poly-T probing, gene-specific dot blot and Northern blots using control probes G3PDH, actin and histone H4. Using mRNA blots 13/20 surgical HCC pairs did not overexpress G3PDH. Those 7/20 intact samples which did appear to overexpress G3PDH on Northern blot could not be detected by poly-T probing of dot blots. The apparent overexpression was not specific for the control gene G3PDH nor for the malignancy HCC. It may represent partial mRNA degradation, or the presence of as yet unknown substances which interfere with absorption at 260/280 nm. We advise caution in selecting human T/N pairs for differential gene expression studies. For HCC, no clinicopathological variables, including cirrhosis, predicted whether a T/N sample pair was likely to be balanced or not.
    No preview · Article · Apr 1998 · International Journal of Oncology
Show more