Anti Proliferative Activity of Caveolin1

Chemo Secrets From a Breast Cancer Survivor

Breast Cancer Survivors

Get Instant Access

Heterologous expression of caveolin-1 in T47-D human mammary cancer cells results in a 50% decrease in growth rate and a three- to 10-fold reduction in anchorage-independent growth [68]. Inhibition of in-vitro anchorage-independent growth, a parameter that is highly correlated with in-vivo tumorigenesis [69], was similarly seen in MCF-7 human breast adenocarcinoma cells [11] and SCLC cells [62]. Caveolin-1 may therefore block a matrix-independent, intrinsic growth signal (e. g., a signal that emanates from an activated oncogene). Indeed, transient transfection with caveolin-1 reduces growth rates in human mammary tumor cells [11,68] and human ovarian carcinoma cells [70]. Accordingly, a mutant caveolin-1 (P132L), identified in about 16% of primary human breast cancer specimens [71], induces morphological transformation in NIH-3T3 cells and supports anchorage-independent growth of mutant-transfected cells [71]. P132L appears to act by causing missorting of normal caveolin-1, leading to its retention at a perinuclear compartment that is probably the Golgi apparatus [72]. It should be noted that the occurrence of the P132L mutation in mammary tumors awaits confirmation in non-Japanese breast cancer patients [73,74]. Further support for its growth-inhibitory action was obtained by analysis of heterozygous and homozygous caveolin-1 knockout mice. Retroviral inactivation of one of the caveolin-1 alleles results in loss of ca. 50% of caveolin-1 expression and enables anchorage-independent growth [75]. Likewise, genetic knockout of caveolin-1 results in hyperplasia of pulmonary endothelial cells and mammary gland epithelial cells [39,40]. Although spontaneous development of mammary or other tumors was not evident in cav-eolin-1-null mice [72], caveolin-1 gene knockout results in increased sensitivity to carcinogenic and oncogenic stimuli [41,42]. Mammary gland tumor-prone MMTV-PyMT mice exhibit accelerated formation of larger and higher-grade dysplastic foci [42]. Long-term mammary tumorigenesis in these mice was doubled and lung metastases were significantly increased [76]. Genetic disruption of caveolin-1 was shown also to cooperate with loss of the tumor suppressor INK4a. This study showed that double knockout of caveolin-1 and INK4a stimulates proliferation of mouse embryo fibroblasts, greatly increases transformation by an activated oncogene (e.g., H-Ras-G12V; v-Src) and results in dramatic stimulation of tumor growth in vivo [77]. Taken together with the heterologous expression data, these results implicate caveolin-1 as an important anti-proliferative protein.

Was this article helpful?

0 0
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment