Differentially Expressed Genes in Two LNCaP Prostate Cancer Cell Lines Reflecting Changes during Prostate Cancer Progression

Abstract

SUMMARY:Prostate cancer tends to become transformed to androgen-independent disease over time when treated by androgen-deprivation therapy. We used two variants of the human prostate cancer cell line LNCaP to study gene expression differences during prostate cancer progression to androgen-independent disease. Production of prostate-specific antigen was regarded as a marker of androgen-dependence and loss of prostate-specific antigen was regarded as a marker of androgenindependence. mRNA from both cell lines was used for cDNA microarray screening. Differential expression of several genes was confirmed by Northern blotting. Monoamine oxidase A, an Expressed Sequence Tag (EST) similar to rat P044, and EST AA412049 were highly overexpressed in androgen-dependent LNCaP cells. Tissue-type plasminogen activator, interferon-inducible protein p78 (MxB), an EST similar to galectin-1, follistatin, fatty acid-binding protein 5, EST AA609749, annexin I, the interferon-inducible gene 1-8U, and phospholipase D1 were highly overexpressed in androgen-independent LNCaP cells. All studied genes had low or no expression in PC-3 cells. The EST similar to rat P044, the EST similar to galectin-1, follistatin, annexin I, and the interferon-inducible gene 1-8U were also expressed in benign prostatic hyperplasia tissue. The Y-linked ribosomal protein S4, Mat-8, and EST AA307912 were highly expressed in benign prostatic hyperplasia tissue. Additionally, both confirmation of differential expression in Northern blots and in situ hybridization were carried out for monoamine oxidase A, the EST similar to rat P044, the EST similar to galectin-1, fatty acid-binding protein 5, and the interferon-inducible gene 1-8U. We identified several potential prostate cancer markers, indicating that the method used is a useful tool for the screening of cancer markers, but other methods, such as in situ hybridization, are needed to further investigate the observations. (Lab Invest 2000, 80:1259-1268.

‘1-8 interferon inducible gene family’: putative colon carcinoma-associated antigens

“…It forms a complex with other proteins and is implicated in cell adhesion and growth inhibitory signals (Deblandre et al, 1995). The 1-8U is expressed in colitis-associated colon cancer and in severely inflamed mucosa in ulcerative colitis (Hisamatsu et al, 1999), as well as in an androgen-independent variant of the prostate carcinoma line LNCaP, but not in an androgen-dependent variant (Vaarala et al, 2000). Interestingly, 1-8D and 9-27 are induced by radiation in a p53-negative line, in an interferonindependent mechanism (Clave et al, 1997).…”

TheTMPRSS2 gene encoding transmembrane serine protease is overexpressed in a majority of prostate cancer patients: Detection of mutatedTMPRSS2 form in a case of aggressive disease

“…However, the LNCaP cell line has been derived from a lymph node metastasis of prostate cancer and the changes in expression detected in LNCaP cells are not comparable to the expression in prostate tissue in every case, as shown in our previous study. 5 Prostate cancer tissue is usually heterogeneous and the presence of androgen-independent clones with characteristics similar to those seen in androgen-independent LNCaP cells thus cannot be excluded.…”

“…5 Here we have extended the expression studies, using in situ hybridization and transcript quantification, to patient samples containing both benign prostate tissue and prostate cancer. Figure 1 shows prostatic expression of TMPRSS2 gene detected by in situ hybridization analysis in endocrine-treated and untreated prostate cancer patients.…”

“…Furthermore, we have identified overexpression of MxA and MxB genes located close to the TMPRSS2 gene at 21q22.3, indicating that this chromosomal locus is vulnerable to regulatory changes during transformation. 5 Nevertheless, this area is not frequently affected by chromosomal rearrangements in prostate cancer. 6,7 However, LNCaP prostate cancer cell line variants do show loss at 21q associated with androgen independence.…”

Response to neoadjuvant treatment in rectal cancer surgery

“…FXYD-3 is a trans-membrane protein normally present in body tissues but overexpressed in several cancers. Increased expression in early tumour differentiation and tumour proliferation has indicated that it could possibly be used as a tumour marker (19,(71)(72)(73)(74)(75). There are also indications that FXYD-3 may be involved in tumour resistance to 5-FU chemotherapy (76).…”