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Isoforms in Cancer
Glycosylation and other post-translational modification pathways in tumor cells are often defective, giving rise to cancer-specific isoforms of normal proteins. For example, CD44 is a cell surface protein known to be mechanistically involved in breast cancer metastasis. While neither RNA levels nor total CD44 protein levels have ever been found to correlate to breast cancer metastasis, increases in the relative abundance of isoform 3 (CD44v3) of the 69 known CD44 isoforms were found to be highly correlated with metastasis to the lymph nodes.9 Isoforms have also been shown to be clinically relevant across wide-ranging applications in cancer care (see table).
| Examples of the Clinical Relevance of Protein Isoforms in Cancer |
Aspect of
Cancer Care
|
Isoform Example |
Diagnosis
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Single PSA isoform is more indicative of cancer than total or free PSA.1
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Staging
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CD44v3 is correlated to breast cancer metastasis where total CD44 protein and mRNA levels are unchanged.2
|
Treatment
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All three chemotherapy agents are ineffective against a specific tubulin isoform, which develops in resistant tumors.3
P-glycoprotein is associated with multi-drug resistance in bladder cancer cells.4 |
Systemic Effects
|
Muscular atrophy in cancer patients is associated with changes in myosin isoforms.5
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Drug Toxicity
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Cytochrome P-450 isoforms are associated with patient-specific drug toxicity.6
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Learn more about Prostate Specific Antigen Isoforms
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1Mikolajczyk et al. (2004), Clin. Biochem. 37:519-528.
2Rys, et al. (2003), Pol. J. Pathol. 54, 243-247.
3Dozier et al, (2003), Breast Cancer Res., 5:R157-69.
4Nakagawa et al. (1997), J. Urol., 157:1260-1264.
5Diffee et al. (2002), Am. J. Physiol. Cell Physiol., 283:C1376-82.
6Piver et al. (2004), Biochem. Pharmacol., 68:773-782.
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