Isolation of a lactoferrin cDNA clone and its expression in human breast cancer

Abstract

Summary A cDNA library constructed from mRNA from a human breast carcinoma metastasis was screened with a polyclonal antibody to deglycosylated human milk fat globule membrane, resulting in the isolation of eight clones from a total of 105 plaques. One of these (J16) was identified as lactoferrin. It was highly expressed (as a 2.5 Kb mRNA) in lactating breast and in both normal resting tissue taken from adjacent to carcinoma or from reduction mammoplasties. Immunoreactive lactoferrin was localised to ductal cells and their secretions in both normal and mildly hyperplastic ducts. In a normal tissue screen J16 was highly expressed in stomach, poorly in skin and lymphocytes and absent from other organs examined. It was variably expressed in 33/59 invasive primary breast tumours; lactoferrin protein in these was heterogeneously distributed in epithelial tumour foci. Presence of J16 was inversely related to expression of oestrogen receptor protein (P = 0.0001). There was no significant relationship to other clinical parameters. We also found immunoreactivity in 20/41 (49%) cases of ductal carcinoma in situ. Expression was not observed in any breast or gastric cell line examined. Thus lactoferrin appears to be down regulated in some forms of cancer. The presence of lactoferrin could be a contraindication for effective endocrine therapy.

Lactotransferrin expression is downregulated and affects the mitogen-activated protein kinase pathway in gastric cancer

“…In addition, the LTF gene is inactivated by genetic and epigenetic mechanisms in lung cancer (24). Previous studies have also indicated that LTF may have a direct effect on tumor cell growth, as suggested by the fact that LTF and an LTF splice variant are downregulated or absent in certain types of cancer (25)(26)(27)(28). The results of the present study indicate that LTF may also serve as an important tumor suppressor gene in GC.…”

Lactoferrin Down-Regulates G1 Cyclin-Dependent Kinases during Growth Arrest of Head and Neck Cancer Cells

“…Lactoferrin exerts an antiproliferative effect on endothelial cells in vitro, and significantly inhibits the vascular endothelial growth factor-mediated angiogenic response in vivo (6). In addition, Campbell et al (7) have shown that lactoferrin may be down-regulated in some cancers, such as human breast carcinoma, and suggested that lactoferrin may regulate cell proliferation. This hypothesis was additionally supported by Damiens et al (8), who demonstrated that treatment of human breast cancer cells with lactoferrin resulted in growth arrest at the G 1 to S transition of the cell cycle and induced an increase in cyclin-dependent kinase (CDK) inhibitor p21 cip1 protein levels by a p53-independent mechanism.…”

Identification of an alternative form of human lactoferrin mRNA that is expressed differentially in normal tissues and tumor-derived cell lines

“…However, in some malignancies, the levels of LF are lower (17,18). In addition, methylation patterns in and around the LF gene are altered in malignant compared with normal breast cells (19).…”