Expression of Com‐1/P8 in human breast cancer and its relevance to clinical outcome and ER status

Abstract

Com‐1 is a recently discovered molecule that has putative action on the metastatic nature of cancer cells. The molecular action and clinical implication in cancer and prognosis are yet to be established. The current study examined the role of Com‐1 in a cohort of patients with breast cancer, with particular emphasis on its relationship with clinical outcomes and ER status. A panel of human breast cancer cell lines were tested. A cohort of breast cancer tumours (n‐120) with matched normal non‐neoplastic mammary tissues (n = 32) were used. Expression of Com‐1 in cancer cells and mammary tissues were studied using conventional and real‐time quantitative PCR. Expression profile was analysed against clinical information including tumour grade, staging, nodal status, ER status and survival of the patients. Statistical analysis was Mann‐Whitney U‐test and Cox Proportion analysis. Com‐1 was expressed in breast cancer cell lines. Com‐1 protein staining was primarily found in nucleus of epithelial cells of mammary tissues. Tumour cells in breast tissues exhibited a significant reduction in nuclear staining of Com‐1, compared to normal epithelial cells (p = 0.0061). Breast tumour tissues expressed similar levels of Com‐1, compared to normal non‐neoplastic mammary tissues (p = 0.62). There was, however, a stepwise decrease in tumours from patients with predicted good, moderate, to poor prognosis (using Nottingham Prognostic Index) (166 ± 135 copies of Com1 transcript, 44.3 ± 36 and 0.64 ± 0.24, respectively, p = 0.06 by Kruskal‐Wallis test). Likewise, node positive tumours had low levels of Com‐1, compared to node negative tumours. Tumours from patients who developed metastasis (11.4 ± 7 copies of Com1 transcript), had local recurrence (41.5 ± 3.7 copies of Com1 transcript), or who died of breast cancer (0.058 ± 0.03 copies of Com1 transcript) had lower levels of Com‐1, when compared to tumours from patients who remained disease free (156 ± 129 copies of Com1 transcript). There was no significant correlation between Com‐1 and overall survival or disease free survival. When ER status were taken into consideration, it was demonstrated that low levels of Com‐1 in ER‐β positive tumours were highly correlated with shorter overall survival of the patients (p = 0.018) (median follow‐up 120 months). Com‐1 is a nuclear protein, whose expression is reduced in human breast cancer tissues and cancer cell lines. The loss of Com‐1 protein is primarily from the nuclear compartment in cancer cells. The expression levels of Com‐1 in breast tumours are correlated with the prognosis of the patients and with the long term overall survival in association with ER status. © 2005 Wiley‐Liss, Inc.

Gene Expression Analysis in HBV Transgenic Mouse Liver: A Model to Study Early Events Related to Hepatocarcinogenesis

“…In particular, a large number of upregulated genes were involved in the modulation of immunological functions, suggesting that the accumulation in the hepatocytes of viral proteins yielded cellular damage followed by an immune response (23,27,29). In addition, several upregulated transcripts have already been correlated to cellular dysplasia and tumor malignancy in different types of cancer (48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58)(59). The microarray data showed the upregulation of NuprI, a transcription factor whose overexpression is inversely correlated with apoptosis in pancreatic cancer (60), and the downregulation of the proapoptotic gene Bnip3 (61,62).…”

PGF isoforms, PLGF-1 and PGF-2 and the PGF receptor, neuropilin, in human breast cancer: Prognostic significance

“…The Q-PCR used was the Amplifluor™ Uniprimer™ system (Intergen Company Oxford, UK) and the Thermo-Start ® (ABgene, Epsom, Surrey, UK), as previously reported (12,13). Specific primers were designed by the authors using Beacon Designers software (Biosoft, Palo Alto, CA, USA) and manufacturated by Invitrogen (Invitrogen Life Technologies, Paisley, UK).…”

“…Sections were counterstained in Gill's haematoxylin and dehydrated in ascending grades of methanol before clearing in xylene and mounting under a cover slip. Semi-quantification of staining intensity was carried out using Optimas package as we previously described (13). Immunohistochemical photographs of normal and tumour sections (n=20) were assessed as previously described (15).…”

Candidate of metastasis 1 regulates in vitro growth and invasion of bladder cancer cells

“…whether it is stimulating or inhibiting may vary in different malignancies. COM1 has been found to aid the establishment of metastasis and to play a key role in the progression of malignancies of breast (1,(5)(6)(7)13), thyroid (4,13,14), central nervous system (15) and pancreas (3,16,17). COM1 has been implicated in inducing chemoresistance in pancreatic and breast cancer cells, protecting them from apoptosis and making tumour cells genetically unstable (17).…”

“…Breast cancer cells have markedly reduced nuclear distribution of the COM1 protein compared with normal mammary epithelial cells. Low levels of COM1 were associated with nodal status and poor clinical outcome (5). A follow-up study showed that the nuclear presence of the COM1 protein was crucial to its inhibitory role in cancer cells, and that loss of its nuclear presence of this molecule had a detrimental effect on its overall negative control of cancer growth (6).…”