Altered expression of organic anion transporter polypeptide (OATP) genes in human breast carcinoma

Abstract

Organic anion transporter polypeptides (OATPs) mediate the transmembrane uptake of endogenous compounds and clinically important drugs in various tissues thereby effecting drug disposition and tissue penetration. OATPs have also been identified in gastric, pancreatic and colon carcinomas but little is known about their expression in breast carcinoma. We therefore analyzed the expression pattern of all 11 known OATPs in three breast cancer cell lines (MCF-7, ZR-75-1, MDA-MB-231) and one immortalized breast epithelial cell line (MCF-10A) using quantitative real-time RT-PCR. Transcripts of 7/11 OATP genes with heterogeneity in their expression profile were detected in control and/or cancer cell lines. Of these seven OATPs, five were also expressed in breast tumor and adjacent non-tumorous specimens from 13 patients. OATP2B1, not found in the analyzed cell lines, was verified in the tissue samples. Interestingly, mRNA expression of OATP2B1, OPATP3A1 and OATP4A1 was significantly higher (p < 0.022) in non-malignant specimens as compared to tumor tissue samples.

Role of Organic Anion-Transporting Polypeptides (OATPs) in Cancer Therapy

“…Certain (60) ↑ in prostate cancer cells (6) qRT-PCR Kidney (64) ↑ in bone cancer (65) RT-PCR OATP1B1 Liver (2,66) ↓ in liver cancer (37)(38)(39)67,68) RT-PCR, IF, IB ↑ in colon polyps and colon cancer (63) RT-PCR ↑ in ovarian cancer (69) RT-PCR OATP1B3 Liver (3,70) ↓ in liver cancer (41) qRT-PCR, IB ↑ in colon cancer (4,71,72) RT-PCR, qRT-PCR, IB, IHC ↑ in pancreatic cancer (71)(72)(73) RT-PCR, qRT-PCR, IB, IHC ↑ in lung cancer (38) RT-PCR, qRT-PCR, IF ↑ in prostate cancer (16,17,68,74) qRT-PCR, IF ↑ in breast cancer (75) qRT-PCR, IHC ↑ in testicular cancer (68) qRT-PCR, IF ↑ in ovarian cancer (69) RT-PCR OATP1C1 Brain (76) ↑ in bone cancers (65) RT-PCR Testes (76) Ciliary body (77) OATP2A1 Ubiquitous (78) ↑ in breast cancer (79) qRT-PCR ↑ in liver cancer (80) qRT-PCR, IF ↑ in bone metastases from kidney cancer (65) qRT-PCR, IB ↓ in cancers of bowel, stomach, ovary, lung, and kidney (81) RT-PCR OATP2B1 Blood-brain barrier (82) ↑ in bone cancer (65) RT-PCR Heart (83) ↑ in breast cancers (79,84) qRT-PCR, IF, IB Enterocytes (85) ↓ in liver and pancreatic cancers (68) qRT-PCR Liver (86) Placenta (87) OATP3A1 Ubiquitous (88) ↑ in bone cysts …”

“…Similar to OATP3A1, OATP4A1 is also overexpressed in multiple cancer cell lines, aneurysmal bone cysts, liver cancers, and breast cancers (65,79,80,90). In colorectal neoplasia specimens, OATP4A1 mRNA levels were reported to be elevated (91).…”

“…Altered expression of OATP2A1 is reported in various types of cancers (Table II). OATP2A1 expression is reported to be increased in breast cancer, HCC, cholangiocarcinoma, and liver metastases from colon cancer (17,79). On the other hand, reduced OATP2A1 levels are reported in other types of cancer from colon, stomach, ovary, lung, and kidneys (81).…”

Influence of Human OATP1B1, OATP1B3, and OATP1A2 on the Pharmacokinetics of Methotrexate and Paclitaxel in Humanized Transgenic Mice

“…6), hepatocellular carcinomas (11), breast carcinomas (13), and lung cancer (12). In addition, expression of OATP1B1 and OATP1A2 was found in malignant breast cell lines (14,43), and OATP1A2 (and OATP2B1) have also been localized in the blood-tumor barrier of gliomas (44). Recently, Takano and colleagues (2009) have shown in vitro that hepatoma cells made resistant to paclitaxel treatment showed, besides increased P-glycoprotein expression, drastically decreased mRNA expression of SLCO1B3 (45).…”

Expression of organic anion-transporting polypeptides 1B1 and 1B3 in ovarian cancer cells: Relevance for paclitaxel transport

“…To facilitate readability and understanding of this manuscript, "OATP" is used for both genes and proteins. OATPs are expressed in a variety of tissues [15] and tumors [16,17], where they mediate the transport of endogenous and exogenous compounds, including drugs [12,13,18]. Studies have shown that uptake transporters can confer sensitivity to anticancer agents [19][20][21][22][23], such as the OATP1B3 substrate methotrexate [19].…”