A notable aberration in the expression of lacritin,
7 the sixth most abundant and one of 29 lacrimal-preferred genes is its reported amplification in some invasive breast cancers.
30 Indeed, the first lacritin EST in GenBank originated from a subtracted breast cancer library.
31 Other novel ESTs now serve as cancer markers.
32 To determine whether any human lacrimal hypothetical or other lacrimal-preferred proteins could be similarly involved in disease, we probed each in the Gene Expression Omnibus (NCBI) paying particular attention to the Cancer Genome Anatomy Project (CGAP) SAGE library
20 21 where lacritin’s cancer expression has been detected. The SAGE library consists of 123 (39 normal, 84 cancer) different human tissue samples, of which 21 are breast and 10 are prostate cancer.
33 Of the 196 lacrimal-expressed hypothetical proteins discussed herein, 104 (53%) display an apparent cancer-associated expression that is at least two times greater than normal in breast, prostate
(Fig. 6) , brain, pancreatic, ovarian, stomach, peritoneal, and other cancers, whereas 47% (93/196) of the same and other hypotheticals display a two times or greater decrease (not shown), depending on the type of cancer. Among lacrimal-preferred genes, 16 (55%) of 29 display a similar twofold or greater increase or decrease. To estimate the frequency of cancer-related changes in expression over the whole lacrimal library, we manually queried the CGAP SAGE library with each of the first 1000 human lacrimal proteins. Of those, 11% (107) displayed a cancer increase or decrease (not shown). FLJ33962, FLJ31208, FLJ20275, and FLJ10101 are unchanged, whereas FLJ25006 (serine/threonine kinase) is increased 2-fold in breast
(Fig. 6)and 12-fold in brain cancers. FLJ20967 (Src homology 2 domain) is increased 5-fold in breast and decreased 22-fold in ovarian (not shown) cancers. DkFZp434N1923 (ubiquitin homologue) displays a 2-, 9-, 14- and 45-fold increase, respectively, in prostate, colon, stomach, and pancreatic cancers. Similarly, Ran binding protein FLJ22794 is suppressed 32-fold in ovarian and amplified 2-, 7-, and 22-fold in brain, colon, and prostate cancers, respectively. FLJ10300 (cytoplasmic dynein intermediate) is increased 6-fold in brain cancer, and the predicted cyclin domain protein FLJ40432, 7- and 16-fold greater in prostate and stomach cancers, respectively. Most elevated in breast cancer is LOC89958, a predicted 389-amino-acid protein of 42.2 kDa that lacks a signal peptide or other defined domain and is 80% (313/389 amino acids) identical with an unknown mouse protein. LOC89958 is well-represented in UniGene by >30 different cancer libraries, including mammary adenocarcinoma, and is periodically regulated during cell cycling in HeLa cells, with maximum mRNA levels during mitosis.
34 Others elevated include FLJ14668 (138 amino acids; DUF842 domain), DKFZp761D0211 (552 amino acids; well conserved with integrin α chain similarity in InterPro, one transmembrane domain and localized to the cell surface) and BC002942 (707 amino acids; 7–11 predicted transmembrane domains; http://ebi.ac.uk/interpro/ provided in the public domain by the European Bioinformatics Institute, Hinxton, UK).